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459 KiB

Open AccessAbstract

NP Navigator: A New Online Tool for the Exploration of the Natural Products Chemical Space

by Yuliana Zabolotna, Peter Ertl, Dragos Horvath, Fanny Bonachera, Gilles Marcou and Alexandre Varnek

Med. Sci. Forum 2021, 7(1), 1; https://doi.org/10.3390/ECMS2021-10829 - 31 Aug 2021

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Abstract

Over the last few billion years, countless organisms populating our planet have produced an extensive reserve of very diverse chemicals called natural products (NPs). Over time, these compounds have evolved to exhibit a wide range of bioactivity and high selectivity in different organisms. [...] Read more.

Over the last few billion years, countless organisms populating our planet have produced an extensive reserve of very diverse chemicals called natural products (NPs). Over time, these compounds have evolved to exhibit a wide range of bioactivity and high selectivity in different organisms. That makes them an extremely important source of potential drugs. However, considering the number of reported NPs and their high diversity, it becomes hard to explore the respective chemical space in drug design. In order to simplify this task, we have developed NP Navigator, a free, user friendly online tool allowing the navigation and analysis of the chemical space of NPs and NP-like compounds [¹,²]. The basis of this tool is a hierarchical ensemble of 241 Generative Topographic Maps (GTM) [³,⁴], visualizing chemical space of NPs from the COlleCtion of Open Natural ProductTs (COCONUT) [⁵], molecules with some biological activity from ChEMBL [⁶], and purchasable compounds from ZINC [⁷]. NP Navigator can be used for an efficient analysis of various aspects of NPs, including calculated properties, chemotype distribution, biological activity, and commercial availability of NPs. Users can browse through hundreds of thousands of molecules from COCONUT, ZINC, and ChEMBL, selecting a zone of interest based on the color code of the maps, which in turn corresponds to specific values of visualized properties. In addition, it is possible to project several external molecules—“chemical trackers”—to trace regions of the NP chemical space containing compounds with desired structural features. In such a manner, the NP Navigator allows searching for NP and NP-like analogues of user-provided compounds. This study was previously published in Molecular Informatics (10.1002/minf.202100068) [¹]. Full article

(This article belongs to the Proceedings of The 1st International Electronic Conference on Molecular Sciences: Druggable Targets of Emerging Infectious Diseases)

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199 KiB

Open AccessAbstract

Potential Protective Activity and Stability of Cornstarch/Chitosan Films Loaded with the Ctx(Ile²¹)-Ha Antimicrobial Peptide †

by Cesar Augusto Roque-Borda, Bruna Fernandes Antunes, Silvio Rainho Teixeira and Eduardo Festozo Vicente

Med. Sci. Forum 2021, 7(1), 2; https://doi.org/10.3390/ECMS2021-10837 - 31 Aug 2021

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Abstract

The high mortality rate of different multi-resistant bacteria (MDR) has led to an immediate and urgent solution. Patients hospitalized for chronic diseases have a weakened immune system and are at high risk of contracting an opportunistic infection. Likewise, the WHO prioritized studies against [...] Read more.

The high mortality rate of different multi-resistant bacteria (MDR) has led to an immediate and urgent solution. Patients hospitalized for chronic diseases have a weakened immune system and are at high risk of contracting an opportunistic infection. Likewise, the WHO prioritized studies against a selected group of MDR bacteria for their control [¹]. In this scope, the Ctx(Ile²¹)-Ha antimicrobial peptide (AMP) presented great potential and efficient biological activity against Acinetobacter baumannii and Pseudomonas aureginosa MDR bacteria [²,³,⁴]. Thus, the aim of this research was to design ultrasound-assisted micro-structured films loaded with the Ctx(Ile²¹)-Ha AMP, based on starch and chitosan, for its effective protective action. Gelling was performed for grain breaking and to expose the hydroxyls [5]. For this, 10 g of cornstarch was used as well as 300 mL of distilled water under agitation at 90 °C for 1 h. Then, 5 mL of the gelled starch was added and mixed with 50 mg of peptide. Then, it was stored in petri dishes at 50 °C for 5 h. Chitosan film was synthesized by free-radical polymerization in the presence of crosslinker [⁶]. Chitosan dispersion (CD) was prepared by dissolving 2% w/v chitosan in 2% v/v acetic acid solution. Ctx(Ile²¹)-Ha was placed on the CD with 0.3% w/v of glycerol and magnetic agitation at 150 rpm. For this, its properties were evaluated by DSC/TGA, FTIR, XRD, and SEM. The physicochemical stability studies of the AMP showed its structure unchanged for up to 3 months exposed to water and for up to one year in the form of a dry film. These results were confirmed by the LC/MS profile, in which XDR indicates a consistent semi-morpho phase. Finally, with these results, we check its stability and protective potential over time and, based on previously published results on their activity against MDR bacteria [²], we conclude that the new products based on AMPs could be potential anti-MDR bacterial agents, avoiding the exposure of critically ill patients in intensive care or post-surgery beds and preventing their dissemination. Full article

(This article belongs to the Proceedings of The 1st International Electronic Conference on Molecular Sciences: Druggable Targets of Emerging Infectious Diseases)

233 KiB

Open AccessAbstract

Pharmacological Properties of Linearolactone against the Amoebiasis Caused by Entamoeba histolytica: An In Silico Study

by Luis Varela-Rodríguez, José Antonio Velázquez-Domínguez, Verónica Ivonne Hernández-Ramírez, Hugo Varela-Rodríguez, Audifas Salvador Matus-Meza, Fernando Calzada, Elihu Bautista and Patricia Talamás-Rohana

Med. Sci. Forum 2021, 7(1), 3; https://doi.org/10.3390/ECMS2021-10843 - 31 Aug 2021

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Abstract

Linearolactone (LL) isolated from Salvia polystachya presents antiparasitic activity against E. histolytica and G. lamblia through ROS production, an apoptosis-like process, and alteration of the actin cytoskeleton. This effect limits the invasion and spread of parasites during host infection. However, the possible toxicological [...] Read more.

Linearolactone (LL) isolated from Salvia polystachya presents antiparasitic activity against E. histolytica and G. lamblia through ROS production, an apoptosis-like process, and alteration of the actin cytoskeleton. This effect limits the invasion and spread of parasites during host infection. However, the possible toxicological effects or the molecular mechanisms by which LL affects the E. histolytica mobility are still not understood. LL could act as an inhibitor of accessory cytoskeletal proteins, such as myosin, calreticulin, and calpain to achieve this end. The aim of this study was to determine the pharmacological and toxicological properties of LL via bioinformatic analyses to find therapeutic targets and to understand the action mechanism on the actin cytoskeleton against E. histolytica. The pharmacological activities, toxicological risks, and molecular targets of LL were determined using free software such as Molsoft© to define the bioactivity through comparison with standard drugs [¹], Molinspiration© to calculate physicochemical properties [²], ToxiM© to determine possible intestinal permeability [³,⁴], SuperCYPsPred© to predict drug metabolism via the cytochrome-P450 system [⁵,⁶], and SEA© to find proteins with binding sites for the active compounds through an inverse protein–ligand approach [⁷,⁸]. Molecular docking with key proteins for the pathogenic activity of E. histolytica trophozoites, such as myosin-II and calreticulin, was performed with AutoDock-Vina and UCSF-Chimera. Results revealed that LL presents a drug-likeness of −0.55 and ToxiM of 0.958 due to medium toxicity associated with interactions in nuclear receptors (0.66), GPCR ligands (0.65), and enzymatic inhibitions (0.47) related to the cytochrome-P450 system (CYP3A4, low). Results indicate that LL is a hydrophobic molecule (LogP: 1.59) with intermediate intestinal absorption (TPSA: 65.75, CACO-2 permeability) and medium blood–brain barrier penetration (3.86). SEA analysis demonstrated that the potential target pharmacophores are OPRK1 (p-Value: 6.49 × 10⁻³⁷, Max TC: 0.49) and NLRP3 (p-Value: 3.90 × 10⁻¹⁹, Max TC: 0.36) in humans. Molecular docking of LL with E. histolytica proteins showed high affinity to ATP-binding catalytic sites in the heavy-chain (GLU-187.A, THR-186.A, ASN-234.B) of myosin-II (−8.30 Kcal/mol), as well as in chain A and C (LYS-199.A, LYS-152.C) of calreticulin (−8.77 Kcal/mol). As for conclusions, LL is a compound with possible moderate toxicity, sedative effects on CNS, and anti-inflammatory properties. In addition, LL has antiparasitic activity involving the immobilization of E. histolytica trophozoites through interactions with accessory proteins from the actin cytoskeleton such as myosin-II and calreticulin. These proteins are present in the parasite and are fundamental to amoebic liver abscess formation during host infection. Therefore, LL could be a therapeutic alternative to the amoebiasis treatment and provide a leading compound for drug discovery against parasitic diseases, but in-depth studies are necessary to confirm these claims. Full article

(This article belongs to the Proceedings of The 1st International Electronic Conference on Molecular Sciences: Druggable Targets of Emerging Infectious Diseases)

2 pages, 172 KiB

Open AccessAbstract

by Dzhuliia Dzhalilova, Anna Kosyreva, Polina Vishnyakova, Ivan Tsvetkov, Natalia Zolotova, Vladimir Mkhitarov and Olga Makarova

Med. Sci. Forum 2021, 7(1), 4; https://doi.org/10.3390/ECMS2021-10831 - 26 Jan 2022

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Abstract

An organism’s hypoxia tolerance depends on many factors, including age. High newborn organism tolerance and high levels of oxidative stress throughout aging have been demonstrated by many studies. However, there is still lack of investigations reflecting the intensity of systemic inflammatory response in [...] Read more.

An organism’s hypoxia tolerance depends on many factors, including age. High newborn organism tolerance and high levels of oxidative stress throughout aging have been demonstrated by many studies. However, there is still lack of investigations reflecting the intensity of systemic inflammatory response in organisms of different ages in correlation to hypoxia tolerance. The aim of this study was to determine the relationship between age-related tolerance to hypoxia, HIF-1 and PHD2 (prolyl hydroxylase domain protein) expression levels and the intensity of systemic inflammatory response in newborn, prepubertal and adult Wistar rats. In case of investigation of the tolerance to hypoxia, rats were placed into a decompression chamber at altitude simulation of 11,500 m. It was demonstrated that prepubertal rats are the least tolerant to hypoxia and newborns are the most tolerant. Newborn rats are characterized by high mRNA Hif-1α expression level in the liver, accompanied by low content of HIF-1 protein and a high level of PHD2. The growth in HIF-1α protein level with age is accompanied by growth in the level of proinflammatory cytokines. Prepubertal animals are the least hypoxia tolerant, and their HIF-1α mRNA expression level was higher than in adult animals. The PHD2 activity in prepubertal animals was significantly reduced in comparison to newborn rats, and the HIF-1α protein level was not changed. The lowest tolerance of the prepubertal males to hypoxia correlated with the greatest manifestations of hepatic inflammation and elevated endotoxin, neopterin, and C-reactive protein levels in LPS-induced systemic inflammatory response. The growth in serum HIF-1α 3 h after LPS injection was observed only in prepubertal rats. The obtained data should be taken into account during the development of a therapeutic strategy for prepubertal children with infectious and inflammatory diseases. Hopefully, this study will provide new insights into age-related differences in tolerance to hypoxia. The possible perspectives of this investigation could be understanding the aspects of HIF-1 mRNA and protein expression in aged animals. Moreover, further studies are required for the identification of additional mechanisms to determine HIF-1α protein level regulation in prepubertal animals. Full article

(This article belongs to the Proceedings of The 1st International Electronic Conference on Molecular Sciences: Druggable Targets of Emerging Infectious Diseases)

164 KiB

Open AccessAbstract

Effects of LSD1 Inhibition on Macrophage Specialization into a Pro-Inflammatory Phenotype

by Magdalena Strachowska, Maciej Sobczak, Karolina Gronkowska and Agnieszka Robaszkiewicz

Med. Sci. Forum 2021, 7(1), 8; https://doi.org/10.3390/ECMS2021-10840 - 31 Aug 2021

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Abstract

Under the influence of many factors, such as cytokines or chemokines, macrophages specialize into two subpopulations: pro-inflammatory M1 (classical pathway) or anti-inflammatory M2 macrophages (alternative pathway). Upon stimulation with the bacterial ligand PAM3CSK4 and upon stimulation with LPS (Lipopolysaccharide), TLR (toll-like receptors) 1/2 [...] Read more.

Under the influence of many factors, such as cytokines or chemokines, macrophages specialize into two subpopulations: pro-inflammatory M1 (classical pathway) or anti-inflammatory M2 macrophages (alternative pathway). Upon stimulation with the bacterial ligand PAM3CSK4 and upon stimulation with LPS (Lipopolysaccharide), TLR (toll-like receptors) 1/2 receptors and TLR4, respectively, activate the NFκB pathway, which leads to the downregulation of catalase expression through the activity of the LSD1 and HDAC1 complex. The main factor responsible for CAT repression is the recruitment of LSD1 and HDAC1 to the promoter site of the gene, resulting in the pausing of RNA polymerase. Inhibition of LSD1 with SP2509 leads to a decreased expression of cytokines such as IL1b and COX2, as well as some surface proteins, e.g., TLR2, despite the presence of LPS. iLSD1 prevents the catalase repression and thereby leads to inhibition of macrophage polarization into the classic pro-inflammatory M1 phenotype. In conclusion, the regulation of catalase expression determines the direction of macrophage specialization. Full article

(This article belongs to the Proceedings of The 1st International Electronic Conference on Molecular Sciences: Druggable Targets of Emerging Infectious Diseases)

188 KiB

Open AccessAbstract

F- and OH-Containing Isopulegol-Derived Octahydro-2H-Chromenes as Agents against Influenza A Virus

by Irina V. Ilyina, Oksana S. Patrusheva, Vladimir V. Zarubaev, Konstantin P. Volcho and Nariman F. Salakhutdinov

Med. Sci. Forum 2021, 7(1), 12; https://doi.org/10.3390/ECMS2021-10836 - 31 Aug 2021

Cited by 1 | Viewed by 710

Abstract

Monoterpenes, which have a unique diverse structure and are inexpensive, available and often enantiomerically pure, are an attractive renewable raw material for the development of physiologically active agents. One of the most important methods for the utilization of monoterpenes is their interaction with [...] Read more.

Monoterpenes, which have a unique diverse structure and are inexpensive, available and often enantiomerically pure, are an attractive renewable raw material for the development of physiologically active agents. One of the most important methods for the utilization of monoterpenes is their interaction with carbonyl compounds, which produces heterocyclic compounds. Often these products exhibit analgesic, antiviral or neuroprotective properties. Earlier, we discovered the anti-influenza A (H1N1) virus activity of several compounds with a hydro-2H-chromene scaffold, which were synthesized by the Prins reaction using p-menthane alcohols and carbonyl compounds; montmorillonite K10 or nanosized halloysite catalyst were used as the reaction catalysts [1]. Chromenols produced from an (–)-isopulegol and aliphatic ketones (acetone and cyclopentanone) demonstrated a high activity combined with a low toxicity against the influenza virus [1]. The introduction of the fluorine atom into the molecule is an important strategy in the development of new biologically active compounds, enabling lipophilicity and electrostatic interactions to change and increasing the metabolic stability of compounds, which affects their physiological activity. Here, we synthesized fluoro- and hydroxy-containing octahydro-2H-chromenes by the Prins reaction starting from an (–)-isopulegol and a wide range of aromatic aldehydes in the presence of the BF₃∙Et₂O/H₂O system, acting as both an acid catalyst and a fluorine source. The activity of the synthesized compounds against the influenza A/Puerto Rico/8/34 (H1N1) virus was studied. The highest activity was demonstrated by fluoro- and hydroxy-containing 2,4,6-trimethoxybenzaldehyde derivatives. These compounds were supposed to be capable of binding to viral hemagglutinin, which is an agreement with data on the effect of compounds on viral fusogenic activity, as well as with molecular docking studies. Full article

(This article belongs to the Proceedings of The 1st International Electronic Conference on Molecular Sciences: Druggable Targets of Emerging Infectious Diseases)

171 KiB

Open AccessAbstract

Morphological Value of Nephrotoxic Effects of Doxorubicin and PLGA-Doxorubicin

by Ivan Tsvetkov, Natalia Zolotova, Anna Kosyreva, Dzhuliia Dzhalilova, Liliya Mikhailova, Vera Kudelkina, Artem Shelkov, Olga Makarova, Valeriy Chernikov and Victoria Razzhivina

Med. Sci. Forum 2021, 7(1), 13; https://doi.org/10.3390/ECMS2021-10834 - 31 Aug 2021

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Abstract

Doxorubicin (DOX) is a chemotherapy drug that causes nephrotoxicity in rodent models and, to a lesser extent, in cancer patients. Doxorubicin hydrochloride or doxorubicin-loaded poly(lactide-co-glycolide acid) (Dox-PLGA) nanoparticles at a therapeutic dose were injected intravenously into male Wistar rats. PLGA is a biodegradable [...] Read more.

Doxorubicin (DOX) is a chemotherapy drug that causes nephrotoxicity in rodent models and, to a lesser extent, in cancer patients. Doxorubicin hydrochloride or doxorubicin-loaded poly(lactide-co-glycolide acid) (Dox-PLGA) nanoparticles at a therapeutic dose were injected intravenously into male Wistar rats. PLGA is a biodegradable polymer used as a drug delivery vehicle. However, the therapeutic effect of Dox-PLGA is not clearly understood. The aim of the study is to estimate a comparative assessment of the nephrotoxic effects of different forms of doxorubicin. This investigation was carried out on male Wistar rats weighing about 200–250 g (n = 24). Morphological assessment of the kidneys was performed using light microscopy. Ultrastructural changes were studied using a TEM Libra120 transmission electron microscope. The levels of ALT, AST, urea, and creatinine in blood serum were determined. Comparison of digital data between experimental groups was performed using the Kruskal–Wallis test (ANOVA). Differences were considered statistically significant at p < 0.05. Degeneration changes in the proximal tubules with the destruction of the brush border were revealed by light and electron microscopy in the kidneys on the 8th and 21st days of the experiment after the administration of doxorubicin hydrochloride and its nanosomal form Dox-PLGA. It was found that on the 8th day, PLGA-doxorubicin causes less pronounced degenerative changes in the epithelium of the proximal tubules. The short-term effect after administration of Dox-PLGA is characterized by an increase in creatinine levels, and the long-term effect by an increase in the level of ALT activity, as well as the concentration of urea and creatinine. Full article

(This article belongs to the Proceedings of The 1st International Electronic Conference on Molecular Sciences: Druggable Targets of Emerging Infectious Diseases)

221 KiB

Open AccessAbstract

LAG-3 Role in Infection

by Luisa Chocarro, Ester Blanco, Hugo Arasanz, Ana Bocanegra, Leticia Fernández-Rubio, Miriam Echaide, Maider Garnica, Pablo Ramos, Grazyna Kochan and David Escors

Med. Sci. Forum 2021, 7(1), 14; https://doi.org/10.3390/ECMS2021-10835 - 31 Aug 2021

Cited by 1 | Viewed by 1010

Abstract

Lymphocyte activation gene 3 (LAG-3) is a cell surface inhibitory receptor with multiple biological activities over T cell activation and effector functions [¹,²,³]. LAG-3 negatively regulates proliferation, activation, effector function and homeostasis of both CD4 and CD8 [...] Read more.

Lymphocyte activation gene 3 (LAG-3) is a cell surface inhibitory receptor with multiple biological activities over T cell activation and effector functions [¹,²,³]. LAG-3 negatively regulates proliferation, activation, effector function and homeostasis of both CD4 and CD8 T cells. LAG-3 plays a regulatory role in immunity and emerged some time ago as an inhibitory immune checkpoint molecule, especially as a potential next-generation target for anti-cancer-targeted therapies. A systematic research was performed using the PubMed and ClinicalTrial.gov databases. Articles published up to 2021 meeting the inclusion criteria were investigated. LAG-3 expression has been linked to increased pathology in certain infections, such as the ones caused by Salmonella, Plasmodium parasites, Mycobacterium tuberculosis, human immunodeficiency virus (HIV), non-pathogenic simian immunodeficiency virus (SIV), in hepatitis B virus (HBV), human papillomavirus (HPV), chronic hepatitis C virus (HCV), lymphocytic choriomeningitis virus (LCMV) and herpes simplex virus 1 (HSV-1) [⁴,⁵,⁶,⁷,⁸,⁹,¹⁰,¹¹,¹²]. Its upregulation in infection is usually associated with a high viral and bacterial load and a reduced survival rate, correlating with faster disease progression and a suppression of viral-specific, T cell-mediated immunity [⁶,⁸,¹²]. LAG-3 inhibits cell proliferation, cytotoxicity function, and cytokine production in response to infection [¹³]. For example, LAG-3 expression is significantly upregulated in hepatitis B virus (HBV)-specific CD8 T cells, acting as a suppressor of HBV-specific, cell-mediated immunity or even to the pathogenesis of hepatocellular carcinoma [⁷,¹²], and it enhances high bacterial burdens together with changes in Th1 responses during active Mycobacterium tuberculosis infections, with an increased expression in the lungs and particularly within the granulomatous lesions [¹⁰]. It also correlates with a high viral load within T cell exhausted cells in HIV infection [⁶]. Here, we will discuss the impaired control of cell-mediated immunity associated with the high accumulation of LAG-3 after infection in most cases associated with a high bacterial/viral load, a reduced survival rate or persisting metabolic and inflammation disorders. Interestingly, the in vitro blockade of PD-1/LAG-3 interactions enhanced cytokine production in response to some of these infections. Full article

(This article belongs to the Proceedings of The 1st International Electronic Conference on Molecular Sciences: Druggable Targets of Emerging Infectious Diseases)

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1149 KiB

Open AccessProceeding Paper

Naturally Occurring Green Tea Polyphenols as Anti-Mycobacterial Agents

by Suraj N. Mali and Anima Pandey

Med. Sci. Forum 2021, 7(1), 5; https://doi.org/10.3390/ECMS2021-10844 - 31 Aug 2021

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Abstract

Tuberculosis (TB) is a global health burden especially in tropical countries. Extensive increments in MDR (Multidrug resistance (MDR): Resistance to at least both isoniazid and rifampicin.) and XDR (Extensive drug resistance (XDR): Resistance to any fluoroquinolone, and at least one of three second-line [...] Read more.

Tuberculosis (TB) is a global health burden especially in tropical countries. Extensive increments in MDR (Multidrug resistance (MDR): Resistance to at least both isoniazid and rifampicin.) and XDR (Extensive drug resistance (XDR): Resistance to any fluoroquinolone, and at least one of three second-line injectable drugs (capreomycin, kanamycin, and amikacin), in addition to multidrug resistance) tuberculosis highlights the ineffectiveness of established anti-TB agents. There is an urgent necessity to identify potent anti-TB agents with unique mechanisms. Green tea and Black tea polyphenols have great potential to inhibit viruses including SARS-COV-2, bacterial strains, etc. In this context, we have screened and identified 65 Green tea bioactive compounds against four mycobacterial pantothenate synthetase and enoyl acyl carrier enzymes. Our molecular docking results revealed that Theaflavin-3-gallate had a higher binding affinity against 2X22 and 3IVX targets with docking scores of −134.13 and −135.592 Kcal/mol, respectively. Furthermore, our molecular dynamics simulations for 10 ns resulted better stabilities of these complexes. We also evaluated in silico drug-likeness and toxicity profiles for the studied polyphenols. Our in silico toxicity analysis suggested that these polyphenols would exhibit lesser toxicity such as eye corrosion, skin irritations, etc. Thus, our present study would provide better insights on studying naturally occurring polyphenols as potential anti-TB agents. Full article

(This article belongs to the Proceedings of The 1st International Electronic Conference on Molecular Sciences: Druggable Targets of Emerging Infectious Diseases)

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2099 KiB

Open AccessProceeding Paper

A Probable Anti-COVID Phytochemical (1,7-Bis-(4-hydroxyphenyl)-1-heptene-3,5-dione) Screened Computationally from the Rhizome of Curcuma longa

by Timothy P. C. Ezeorba, Nene O. Uchendu, Ekene J. Nweze, Chibuzo K. Okoroafor, Pascal O. Ogbu, Miracle C. Okpara, Rita O. Asomadu and Parker E. Joshua

Med. Sci. Forum 2021, 7(1), 6; https://doi.org/10.3390/ECMS2021-10845 - 31 Aug 2021

Cited by 2 | Viewed by 1482

Abstract

The devastating nature of the SARS-CoV-2 pandemic has fostered the need for potent therapeutics to manage or curb the disease’s severity. As a response, several studies on drug repurposing, vaccine design and optimizing natural phytochemicals are ongoing. This study aims at screening for [...] Read more.

The devastating nature of the SARS-CoV-2 pandemic has fostered the need for potent therapeutics to manage or curb the disease’s severity. As a response, several studies on drug repurposing, vaccine design and optimizing natural phytochemicals are ongoing. This study aims at screening for potent and novel anti-COVID phytochemicals from the rhizome of Curcuma longa. A phytochemical library of 50 nonubiquitous bioactive compounds from the rhizome of Curcuma longa was retrieved from Dr. Duke’s phytochemical and ethnobotanical database (accessed on 20 April 2021). The compounds in the library were docked against the receptor binding domain (RBD) of SARS-CoV-2 (PDB ID: 7EAM_1). Three compounds—quercetin; 1,7-Bis-(4-hydroxyphenyl)-1-heptene-3,5-dione; and cyclocurcumin, were selected based on their higher docking score than the standard repurposed drug (Arbidol). This study further examined the interactions of the novel 1,7-Bis-(4-hydroxyphenyl)-1-heptene-3,5-dione (BHHD) in the binding pocket as well as its ADMET properties. Excellent interaction was observed between the atoms of BHHD and amino acid residues known to foster the viral entry into the host. Furthermore, the ADMET result for BHHD was impressive for a lead molecule. Therefore, this study recommends for further investigation on the potency and toxicity of BHHD both on cell lines and animal models. Full article

(This article belongs to the Proceedings of The 1st International Electronic Conference on Molecular Sciences: Druggable Targets of Emerging Infectious Diseases)

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437 KiB

Open AccessProceeding Paper

Anti-Nematodal Essential Oils with Activity against Anisakis

by Jorge M. S. Faria and Inês V. da Silva

Med. Sci. Forum 2021, 7(1), 7; https://doi.org/10.3390/ECMS2021-10827 - 31 Aug 2021

Viewed by 1995

Abstract

Anisakiasis is a human parasitic infection caused by the larvae of the Anisakis nematode through the consumption of raw or undercooked seafood, namely fish and cephalopods. To date, no effective drug has been uncovered and common anthelmintic treatments seem to have reduced activity [...] Read more.

Anisakiasis is a human parasitic infection caused by the larvae of the Anisakis nematode through the consumption of raw or undercooked seafood, namely fish and cephalopods. To date, no effective drug has been uncovered and common anthelmintic treatments seem to have reduced activity against this parasite. Essential oils (EOs) are an unexplored source of natural products able to counteract Anisakis. The present work reviews the available literature on EOs tested in vitro against Anisakis nematodes and compiles the activity and composition of the most active EOs. Over a dozen plant species were used as sources of EOs, mainly from the Asteraceae, Lamiaceae, Apiaceae and Myrtaceae families. The lowest half maximal effective concentrations (EC₅₀) were reported for Origanum syriacum and O. compactum EOs, both rich in carvacrol (83% and 50%, respectively). The EOs extracted from Tagetes minuta and Nepeta cataria were reported as the fastest acting, with half maximal effective times (ET₅₀) under 4 h, and were rich in geraniol (55%) or β-ocimene (36%) and limonene (27%), respectively. Given their complex chemical composition, additive, synergistic and antagonistic interactions between EO compounds can be responsible for EO activity. A deeper analysis of the chemical structures that are active against Anisakis, and the nature of their interactions, can be unveiled with further studies on this parasitosis. Full article

(This article belongs to the Proceedings of The 1st International Electronic Conference on Molecular Sciences: Druggable Targets of Emerging Infectious Diseases)

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728 KiB

Open AccessProceeding Paper

Benzothiazole Moiety and Its Derivatives as Antiviral Agents

by Khyati Bhagdev and Sibaji Sarkar

Med. Sci. Forum 2021, 7(1), 9; https://doi.org/10.3390/ECMS2021-10839 - 31 Aug 2021

Cited by 3 | Viewed by 1751

Abstract

A virus is a microorganism that uses the machinery of the host to multiply. At present, there are various species of viruses known to us that are dangerous for the health of human beings. One of such viruses has destroyed many lives nowadays [...] Read more.

A virus is a microorganism that uses the machinery of the host to multiply. At present, there are various species of viruses known to us that are dangerous for the health of human beings. One of such viruses has destroyed many lives nowadays and that is a coronavirus. Such other viruses like Human Immunodeficiency Virus, Poliovirus, etc., destroy one’s capability to survive normally. As science progresses, we invent many antiviral drugs as per the type of virus. There are many antiviral drugs available to treat viral infections. From them, benzothiazole derivatives are potent antiviral agents. Researchers continuously work on benzothiazole moiety to get more effective benzothiazole derivatives that can be used as antiviral agents. This review article gives information about various benzothiazole derivatives that are invented during 1980 to 2021, that act against the various viruses as antiviral agents, the structure–activity relationship of benzothiazole as an antiviral agent, various schemes to synthesize benzothiazole derivatives as an antiviral agent as well as includes various methods to evaluate the antiviral activity of novel synthetic compounds against specific viruses. Full article

(This article belongs to the Proceedings of The 1st International Electronic Conference on Molecular Sciences: Druggable Targets of Emerging Infectious Diseases)

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276 KiB

Open AccessProceeding Paper

Biocidal Cationic Macromolecules Irrespective of Bacterial Resistance: Our Best Achievements

by Silvana Alfei, Gabriella Piatti, Debora Caviglia, Gian Carlo Schito, Guendalina Zuccari and Anna Maria Schito

Med. Sci. Forum 2021, 7(1), 10; https://doi.org/10.3390/ECMS2021-10833 - 31 Aug 2021

Cited by 1 | Viewed by 1015

Abstract

Since new antibacterial agents against multi-drug resistant (MDR) bacteria are urgently needed, we recently synthetized cationic dendrimers and copolymers and assessed their antibacterial activity on numerous MDR clinical isolates. Being cationic, the prepared macromolecules electrostatically interacted with pathogens’ surfaces, causing irreversible damages and [...] Read more.

Since new antibacterial agents against multi-drug resistant (MDR) bacteria are urgently needed, we recently synthetized cationic dendrimers and copolymers and assessed their antibacterial activity on numerous MDR clinical isolates. Being cationic, the prepared macromolecules electrostatically interacted with pathogens’ surfaces, causing irreversible damages and rapid bacterial death. A lysine dendrimer having 192 cationic groups (N⁺) was strongly active preferentially on non-fermenting Gram-negative species, displaying MICs comparable to colistin against P. aeruginosa (2.1 µM). A lysine dendrimer (128 N⁺) was explicitly active on Acinetobacter, while a cationic copolymer showed remarkable antibacterial activity against numerous Gram-positive and Gram-negative species. In 24 h-time-killing experiments, all of the mentioned macromolecules displayed rapid bactericidal effects, while when tested on human keratinocytes, especially G5-PDK, showed low levels of cytotoxicity and high values of selectivity indices. Due to their physicochemical properties and bactericidal potency, the herein reviewed cationic macromolecules could represent novel tools for realizing either a targeted or a broad-spectrum bactericidal action, regardless of the bacterial resistance to current antibiotics. Full article

(This article belongs to the Proceedings of The 1st International Electronic Conference on Molecular Sciences: Druggable Targets of Emerging Infectious Diseases)

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9 pages, 266 KiB

Open AccessProceeding Paper

The Impacts of Anti-Inflammatory Agents on COVID-19 Cytokine Storm

by Ifeoma Felicia Chukwuma, Victor Onukwube Apeh, Florence Nkechi Nworah, Chidi Augustine Madueke and Valentine Odirachukwumma Nwanelo

Med. Sci. Forum 2021, 7(1), 11; https://doi.org/10.3390/ECMS2021-10910 - 30 Sep 2021

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Abstract

The re-emergence of severe acute respiratory syndrome coronavirus 2 A(SARS-CoV-2) in Wuhan, China, has placed an unprecedented economic and health burden globally. The SARS-CoV-2 high mortality rate has brought great challenges to researchers, clinicians, and health workers in their bid to discover appropriate [...] Read more.

The re-emergence of severe acute respiratory syndrome coronavirus 2 A(SARS-CoV-2) in Wuhan, China, has placed an unprecedented economic and health burden globally. The SARS-CoV-2 high mortality rate has brought great challenges to researchers, clinicians, and health workers in their bid to discover appropriate therapeutic interventions. The search for the ultimate remedy was initially centered on the use of antiviral agents targeting receptors and proteins involved in the pathophysiology of SARS-CoV-2. However, the upsurge of interest in repurposing anti-inflammatory agents was born out of the reported risks posed by a cytokine storm on COVID-19-induced fatality. A cytokine storm, as a result of the unregulated production of pro-inflammatory cytokines and other chemical mediators, triggers coagulopathy, viral sepsis, pneumonitis shock, and acute respiratory syndrome, which may lead directly to respiratory and organ failure and ultimately the death of the patient. The overwhelming evidence has shown that the early prediction of cytokine storm using serum chemistry and hematological markers and the use of appropriate anti-inflammatory agents will avert COVID-19 complications. These include the use of repurposed interferon (IFN) therapy and inhibitors of interleukin-1 (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and Janus kinase (JAKs) to nip the cytokine storm in the bud. This review critically used information retrieved from PubMed, China National Knowledge Infrastructure, Embase, Medline, and Google Scholar to elaborate on the mechanism and complications of COVID-19 cytokine storm, therapeutic interventions, and the way forward to discovering effective biocompatible drug targets. Full article

(This article belongs to the Proceedings of The 1st International Electronic Conference on Molecular Sciences: Druggable Targets of Emerging Infectious Diseases)

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