Antibiotics

Research

Jump to: Review

17 pages, 3599 KiB

Open AccessArticle

Computer-Aided Drug Design and Synthesis of Rhenium Clotrimazole Antimicrobial Agents

by Youri Cortat, Miroslava Nedyalkova, Kevin Schindler, Parth Kadakia, Gozde Demirci, Sara Nasiri Sovari, Aurelien Crochet, Stefan Salentinig, Marco Lattuada, Olimpia Mamula Steiner and Fabio Zobi

Antibiotics 2023, 12(3), 619; https://doi.org/10.3390/antibiotics12030619 - 20 Mar 2023

Cited by 8 | Viewed by 3118

Abstract

In the context of the global health issue caused by the growing occurrence of antimicrobial resistance (AMR), the need for novel antimicrobial agents is becoming alarming. Inorganic and organometallic complexes represent a relatively untapped source of antibiotics. Here, we report a computer-aided drug [...] Read more.

In the context of the global health issue caused by the growing occurrence of antimicrobial resistance (AMR), the need for novel antimicrobial agents is becoming alarming. Inorganic and organometallic complexes represent a relatively untapped source of antibiotics. Here, we report a computer-aided drug design (CADD) based on a ‘scaffold-hopping’ approach for the synthesis and antibacterial evaluation of fac-Re(I) tricarbonyl complexes bearing clotrimazole (ctz) as a monodentate ligand. The prepared molecules were selected following a pre-screening in silico analysis according to modification of the 2,2′-bipyridine (bpy) ligand in the coordination sphere of the complexes. CADD pointed to chiral 4,5-pinene and 5,6-pinene bipyridine derivatives as the most promising candidates. The corresponding complexes were synthesized, tested toward methicillin-sensitive and -resistant S. aureus strains, and the obtained results evaluated with regard to their binding affinity with a homology model of the S. aureus MurG enzyme. Overall, the title species revealed very similar minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values as those of the reference compound used as the scaffold in our approach. The obtained docking scores advocate the viability of ‘scaffold-hopping’ for de novo design, a potential strategy for more cost- and time-efficient discovery of new antibiotics. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Antimicrobial Agents)

► Show Figures

Graphical abstract

31 pages, 8725 KiB

Open AccessArticle

QSAR Studies, Molecular Docking, Molecular Dynamics, Synthesis, and Biological Evaluation of Novel Quinolinone-Based Thiosemicarbazones against Mycobacterium tuberculosis

by Jhesua Valencia, Vivian Rubio, Gloria Puerto, Luisa Vasquez, Anthony Bernal, José R. Mora, Sebastian A. Cuesta, José Luis Paz, Braulio Insuasty, Rodrigo Abonia, Jairo Quiroga, Alberto Insuasty, Andres Coneo, Oscar Vidal, Edgar Márquez and Daniel Insuasty

Antibiotics 2023, 12(1), 61; https://doi.org/10.3390/antibiotics12010061 - 29 Dec 2022

Cited by 8 | Viewed by 3507

Abstract

In this study, a series of novel quinolinone-based thiosemicarbazones were designed in silico and their activities tested in vitro against Mycobacterium tuberculosis (M. tuberculosis). Quantitative structure-activity relationship (QSAR) studies were performed using quinolinone and thiosemicarbazide as pharmacophoric nuclei; the best model [...] Read more.

In this study, a series of novel quinolinone-based thiosemicarbazones were designed in silico and their activities tested in vitro against Mycobacterium tuberculosis (M. tuberculosis). Quantitative structure-activity relationship (QSAR) studies were performed using quinolinone and thiosemicarbazide as pharmacophoric nuclei; the best model showed statistical parameters of R² = 0.83; F = 47.96; s = 0.31, and was validated by several different methods. The van der Waals volume, electron density, and electronegativity model results suggested a pivotal role in antituberculosis (anti-TB) activity. Subsequently, from this model a new series of quinolinone-thiosemicarbazone 11a–e was designed and docked against two tuberculosis protein targets: enoyl-acyl carrier protein reductase (InhA) and decaprenylphosphoryl-β-D-ribose-2’-oxidase (DprE1). Molecular dynamics simulation over 200 ns showed a binding energy of −71.3 to −12.7 Kcal/mol, suggesting likely inhibition. In vitro antimycobacterial activity of quinolinone-thiosemicarbazone for 11a–e was evaluated against M. bovis, M. tuberculosis H37Rv, and six different strains of drug-resistant M. tuberculosis. All compounds exhibited good to excellent activity against all the families of M. tuberculosis. Several of the here synthesized compounds were more effective than the standard drugs (isoniazid, oxafloxacin), 11d and 11e being the most active products. The results suggest that these compounds may contribute as lead compounds in the research of new potential antimycobacterial agents. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Antimicrobial Agents)

► Show Figures

Figure 1

20 pages, 2529 KiB

Open AccessArticle

Synthesis, Physicochemical Properties and Molecular Docking of New Benzothiazole Derivatives as Antimicrobial Agents Targeting DHPS Enzyme

by Rasha A. Azzam, Heba A. Elboshi and Galal H. Elgemeie

Antibiotics 2022, 11(12), 1799; https://doi.org/10.3390/antibiotics11121799 - 11 Dec 2022

Cited by 9 | Viewed by 2002

Abstract

The drug-resistance problem is widely spread and becoming more common in community-acquired and nosocomial strains of bacteria. Therefore, finding new antimicrobial agents remains an important drug target. From this perspective, new derivatives of benzothiazole were synthesized and evaluated for their antimicrobial activity and [...] Read more.

The drug-resistance problem is widely spread and becoming more common in community-acquired and nosocomial strains of bacteria. Therefore, finding new antimicrobial agents remains an important drug target. From this perspective, new derivatives of benzothiazole were synthesized and evaluated for their antimicrobial activity and ability to inhibit the DHPS enzyme. The synthesis was carried out by the reaction of benzothiazole N-arylsulphonylhydrazone with N-aryl-2-cyano-3-(dimethylamino)acrylamide, N-aryl-3-(dimethylamino)prop-2-en-1-one, arylaldehydes or diazonium salt of arylamine derivatives, which led to the formation of N-arylsulfonylpyridones 6a–d (yield 60–70%) and 12a–c (yield 50–60%),N-(2-(benzo[d]thiazole-2-yl)-3-arylacryloyl-4-methylsulfonohydrazide 14a–c (yield 60–65%), 4-(benzo[d]thiazole-2-yl)-5-aryl-1H-pyrazol-3(2H)-one 16a–c (yield 65–75%), and N′-(2-(benzo[d]thiazol-2-yl)-2-(2-arylhydrazono)acetyl)-4-arylsulfonohydrazide 19a–e (yield 85–70%). The antimicrobial evaluations resulted into a variety of microbial activities against the tested strains. Most compounds showed antimicrobial activity against S. aureus with an MIC range of 0.025 to 2.609 mM. The most active compound, 16c, exhibited superior activity against the S. aureus strain with an of MIC 0.025 mM among all tested compounds, outperforming both standard drugs ampicillin and sulfadiazine. The physicochemical–pharmacokinetic properties of the synthesized compounds were studied, and it was discovered that some compounds do not violate rule of five and have good bioavailability and drug-likeness scores. The five antimicrobial potent compounds with good physicochemical–pharmacokinetic properties were then examined for their inhibition of DHPS enzyme. According to the finding, three compounds, 16a–c, had IC₅₀ values comparable to the standard drug and revealed that compound 16b was the most active compound with an IC₅₀ value of 7.85 μg/mL, which is comparable to that of sulfadiazine (standard drug) with an IC₅₀ value of 7.13 μg/mL. A docking study was performed to better understand the interaction of potent compounds with the binding sites of the DHPS enzyme, which revealed that compounds 16a–c are linked by two arene-H interactions with Lys220 within the PABA pocket. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Antimicrobial Agents)

► Show Figures

Figure 1

13 pages, 1355 KiB

Open AccessArticle

The Potential of Phenothiazines against Endodontic Pathogens: A Focus on Enterococcus-Candida Dual-Species Biofilm

by Nicole de Mello Fiallos, Ana Luiza Ribeiro Aguiar, Bruno Nascimento da Silva, Mariana Lara Mendes Pergentino, Marcos Fábio Gadelha Rocha, José Júlio Costa Sidrim, Débora Castelo Branco de Souza Collares Maia and Rossana de Aguiar Cordeiro

Antibiotics 2022, 11(11), 1562; https://doi.org/10.3390/antibiotics11111562 - 5 Nov 2022

Cited by 4 | Viewed by 2126

Abstract

Persistent apical periodontitis occurs when the endodontic treatment fails to eradicate the intraradicular infection, and is mainly caused by Gram-positive bacteria and yeasts, such as Enterococcus faecalis and Candida albicans, respectively. Phenothiazines have been described as potential antimicrobials against bacteria and fungi. [...] Read more.

Persistent apical periodontitis occurs when the endodontic treatment fails to eradicate the intraradicular infection, and is mainly caused by Gram-positive bacteria and yeasts, such as Enterococcus faecalis and Candida albicans, respectively. Phenothiazines have been described as potential antimicrobials against bacteria and fungi. This study aimed to investigate the antimicrobial potential of promethazine (PMZ) and chlorpromazine (CPZ) against E. faecalis and C. albicans dual-species biofilms. The susceptibility of planktonic cells to phenothiazines, chlorhexidine (CHX) and sodium hypochlorite (NaOCl) was initially analyzed by broth microdilution. Interaction between phenothiazines and CHX was examined by chequerboard assay. The effect of NaOCl, PMZ, CPZ, CHX, PMZ + CHX, and CPZ + CHX on biofilms was investigated by susceptibility assays, biochemical and morphological analyses. Results were evaluated through one-way ANOVA and Tukey’s multiple comparison post-test. PMZ, alone or in combination with irrigants, was the most efficient phenothiazine, capable of reducing cell counts, biomass, biovolume, carbohydrate and protein contents of dual-species biofilms. Neither PMZ nor CPZ increased the antimicrobial activity of CHX. Further investigations of the properties of phenothiazines should be performed to encourage their use in endodontic clinical practice. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Antimicrobial Agents)

► Show Figures

Figure 1

27 pages, 6259 KiB

Open AccessArticle

Synergic Effect of Phthalide Lactones and Fluconazole and Its New Analogues as a Factor Limiting the Use of Azole Drugs against Candidiasis

by Piotr Krężel, Teresa Olejniczak, Aleksandra Tołoczko, Joanna Gach, Marek Weselski and Robert Bronisz

Antibiotics 2022, 11(11), 1500; https://doi.org/10.3390/antibiotics11111500 - 28 Oct 2022

Cited by 2 | Viewed by 2019

Abstract

The resistance of Candida albicans and other pathogenic yeasts to azole antifungal drugs has increased rapidly in recent years and is a significant problem in clinical therapy. The current state of pharmacological knowledge precludes the withdrawal of azole drugs, as no other active [...] Read more.

The resistance of Candida albicans and other pathogenic yeasts to azole antifungal drugs has increased rapidly in recent years and is a significant problem in clinical therapy. The current state of pharmacological knowledge precludes the withdrawal of azole drugs, as no other active substances have yet been developed that could effectively replace them. Therefore, one of the anti-yeast strategies may be therapies that can rely on the synergistic action of natural compounds and azoles, limiting the use of azole drugs against candidiasis. Synergy assays performed in vitro were used to assess drug interactions Fractional Inhibitory Concentration Index. The synergistic effect of fluconazole (1) and three synthetic lactones identical to those naturally occurring in celery plants—3-n-butylphthalide (2), 3-n-butylidenephthalide (3), 3-n-butyl-4,5,6,7-tetrahydrophthalide (4)—against Candida albicans ATCC 10231, C. albicans ATCC 2091, and C. guilliermondii KKP 3390 was compared with the performance of the individual compounds separately. MIC₉₀ (the amount of fungistatic substance (in µg/mL) inhibiting yeast growth by 90%) was determined as 5.96–6.25 µg/mL for fluconazole (1) and 92–150 µg/mL for lactones 2–4. With the simultaneous administration of fluconazole (1) and one of the lactones 2–4, it was found that they act synergistically, and to achieve the same effect it is sufficient to use 0.58–6.73 µg/mL fluconazole (1) and 1.26–20.18 µg/mL of lactones 2–4. As fluconazole and phthalide lactones show synergy, 11 new fluconazole analogues with lower toxicity and lower inhibitory activity for CYP2C19, CYP1A2, and CYP2C9, were designed after in silico testing. The lipophilicity was also analyzed. A three-carbon alcohol with two rings was preserved. In all compounds 5–15, the 1,2,4-triazole rings were replaced with 1,2,3-triazole or tetrazole rings. The hydroxyl group was free or esterified with phenylacetic acid or thiophene-2-carboxylic acid chlorides or with adipic acid. In structures 11 and 12 the hydroxyl group was replaced with the fragment -CH₂Cl or = CH₂. Additionally, the difluorophenyl ring was replaced with unsubstituted phenyl. The structures of the obtained compounds were determined by ¹H NMR, and ¹³C NMR spectroscopy. Molecular masses were established by GC-MS or elemental analysis. The MIC₅₀ and MIC₉₀ of all compounds 1–15 were determined against Candida albicans ATCC 10231, C. albicans ATCC 2091, AM 38/20, C. guilliermondii KKP 3390, and C. zeylanoides KKP 3528. The MIC₅₀ values for the newly prepared compounds ranged from 38.45 to 260.81 µg/mL. The 90% inhibitory dose was at least twice as high. Large differences in the effect of fluconazole analogues 5–15 on individual strains were observed. A synergistic effect on three strains—Candida albicans ATCC 10231, C. albicans ATCC 2091, C. guilliermondii KKP 339—was observed. Fractional inhibitory concentrations FIC₅₀ and FIC₉₀ were tested for the most active lactone, 3-n-butylphthalide, and seven fluconazole analogues. The strongest synergistic effect was observed for the strain C. albicans ATCC 10231, FIC 0.04–0.48. The growth inhibitory amount of azole is from 25 to 55 µg/mL and from 3.13 to 25.3 µg/mL for 3-n-butylphthalide. Based on biological research, the influence of the structure on the fungistatic activity and the synergistic effect were determined. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Antimicrobial Agents)

► Show Figures

Graphical abstract

23 pages, 3452 KiB

Open AccessArticle

Synthetic Flavonoid BrCl-Flav—An Alternative Solution to Combat ESKAPE Pathogens

by Cristina-Veronica Moldovan, Mihaela Savu, Elodie Dussert, Haïrati Aboubacar, Laura Gabriela Sarbu, Simona Matiut, Benoit Cudennec, François Krier, Rozenn Ravallec, Lucian Mihail Birsa and Marius Stefan

Antibiotics 2022, 11(10), 1389; https://doi.org/10.3390/antibiotics11101389 - 11 Oct 2022

Cited by 4 | Viewed by 2606

Abstract

ESKAPE pathogens are considered as global threats to human health. The discovery of new molecules for which these pathogens have not yet developed resistance is a high medical priority. Synthetic flavonoids are good candidates for developing new antimicrobials. Therefore, we report here the [...] Read more.

ESKAPE pathogens are considered as global threats to human health. The discovery of new molecules for which these pathogens have not yet developed resistance is a high medical priority. Synthetic flavonoids are good candidates for developing new antimicrobials. Therefore, we report here the potent in vitro antibacterial activity of BrCl-flav, a representative of a new class of synthetic tricyclic flavonoids. Minimum inhibitory/bactericidal concentration, time kill and biofilm formation assays were employed to evaluate the antibacterial potential of BrCl-flav. The mechanism of action was investigated using fluorescence and scanning electron microscopy. A checkerboard assay was used to study the effect of the tested compound in combination with antibiotics. Our results showed that BrCl-flav displayed important inhibitory activity against all tested clinical isolates, with MICs ranging between 0.24 and 125 µg/mL. A total kill effect was recorded after only 1 h of exposing Enterococcus faecium cells to BrCl-flav. Additionally, BrCl-flav displayed important biofilm disruption potential against Acinetobacter baumannii. Those effects were induced by membrane integrity damage. BrCl-flav expressed synergistic activity in combination with penicillin against a MRSA strain. Based on the potent antibacterial activity, low cytotoxicity and pro-inflammatory effect, BrCl-flav has good potential for developing new effective drugs against ESKAPE pathogens. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Antimicrobial Agents)

► Show Figures

Graphical abstract

19 pages, 9657 KiB

Open AccessArticle

Azole-Based Compounds That Are Active against Candida Biofilm: In Vitro, In Vivo and In Silico Studies

by Simone Carradori, Alessandra Ammazzalorso, Barbara De Filippis, Ahmet Fatih Şahin, Atilla Akdemir, Anastasia Orekhova, Graziana Bonincontro and Giovanna Simonetti

Antibiotics 2022, 11(10), 1375; https://doi.org/10.3390/antibiotics11101375 - 8 Oct 2022

Cited by 8 | Viewed by 2547

Abstract

Fungal pathogens, including Candida spp., Aspergillus spp. and dermatophytes, cause more than a billion human infections every year. A large library of imidazole- and triazole-based compounds were in vitro screened for their antifungal activity against C. albicans, C. glabrata, C. krusei [...] Read more.

Fungal pathogens, including Candida spp., Aspergillus spp. and dermatophytes, cause more than a billion human infections every year. A large library of imidazole- and triazole-based compounds were in vitro screened for their antifungal activity against C. albicans, C. glabrata, C. krusei, A. fumigatus and dermatophytes, such as Microsporum gypseum, Trichophyton rubrum and Trichophyton mentagrophytes. The imidazole carbamate 12 emerged as the most active compound, showing a valuable antifungal activity against C. glabrata (MIC 1–16 μg/mL) and C. krusei (MIC 4–24 μg/mL). No activity against A. fumigatus or the dermatophytes was observed among all the tested compounds. The compound 12 inhibited the formation of C. albicans, C. glabrata and C. krusei biofilms and reduced the mature Candida biofilm. In the Galleria mellonella larvae, 12 showed a significant reduction in the Candida infection, together with a lack of toxicity at the concentration used to activate its antifungal activity. Moreover, the in silico prediction of the putative targets revealed that the concurrent presence of the imidazole core, the carbamate and the p-chlorophenyl is important for providing a strong affinity for lanosterol 14α-demethylase (CgCYP51a1) and the fungal carbonic anhydrase (CgNce103), the S-enantiomer being more productive in these interactions. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Antimicrobial Agents)

► Show Figures

Figure 1

25 pages, 5047 KiB

Open AccessArticle

Design, Synthesis and Mechanistic Studies of Novel Isatin-Pyrazole Hydrazone Conjugates as Selective and Potent Bacterial MetAP Inhibitors

by Iram Irfan, Asghar Ali, Bharati Reddi, Mohd. Abrar Khan, Phool Hasan, Sarfraz Ahmed, Amad Uddin, Magdalena Piatek, Kevin Kavanagh, Qazi Mohd. Rizwanul Haque, Shailja Singh, Anthony Addlagatta and Mohammad Abid

Antibiotics 2022, 11(8), 1126; https://doi.org/10.3390/antibiotics11081126 - 19 Aug 2022

Cited by 8 | Viewed by 3073

Abstract

Methionine aminopeptidases (MetAPs) are attractive drug targets due to their essential role in eukaryotes as well as prokaryotic cells. In this study, biochemical assays were performed on newly synthesized Isatin-pyrazole hydrazones (PS1–14) to identify potent and selective bacterial MetAPs inhibitors. [...] Read more.

Methionine aminopeptidases (MetAPs) are attractive drug targets due to their essential role in eukaryotes as well as prokaryotic cells. In this study, biochemical assays were performed on newly synthesized Isatin-pyrazole hydrazones (PS1–14) to identify potent and selective bacterial MetAPs inhibitors. Compound PS9 inhibited prokaryotic MetAPs, i.e., MtMetAP1c, EfMetAP1a and SpMetAP1a with K_i values of 0.31, 6.93 and 0.37 µM, respectively. Interestingly, PS9 inhibited the human analogue HsMetAP1b with Ki (631.7 µM) about ten thousand-fold higher than the bacterial MetAPs. The in vitro screening against Gram-positive (Enterococcus faecalis, Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa, Klebsiella pneumonia and Escherichia coli) bacterial strains also exhibited their antibacterial potential supported by minimum bactericidal concentration (MBC), disk diffusion assay, growth curve and time-kill curve experiments. Additionally, PS6 and PS9 had synergistic effects when combined with ampicillin (AMP) and ciprofloxacin (CIP) against selective bacterial strains. PS9 showed no significant cytotoxic effect on human RBCs, HEK293 cells and Galleria mellonella larvae in vivo. PS9 inhibited the growth of multidrug-resistant environmental isolates as it showed the MIC lower than the standard drugs used against selective bacterial strains. Overall, the study suggested PS9 could be a useful candidate for the development of antibacterial alternatives. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Antimicrobial Agents)

► Show Figures

Figure 1

Review

Jump to: Research

62 pages, 5604 KiB

Open AccessReview

Design and Synthesis of Novel Antimicrobial Agents

by Zeinab Breijyeh and Rafik Karaman

Antibiotics 2023, 12(3), 628; https://doi.org/10.3390/antibiotics12030628 - 22 Mar 2023

Cited by 32 | Viewed by 9174

Abstract

The necessity for the discovery of innovative antimicrobials to treat life-threatening diseases has increased as multidrug-resistant bacteria has spread. Due to antibiotics’ availability over the counter in many nations, antibiotic resistance is linked to overuse, abuse, and misuse of these drugs. The World [...] Read more.

The necessity for the discovery of innovative antimicrobials to treat life-threatening diseases has increased as multidrug-resistant bacteria has spread. Due to antibiotics’ availability over the counter in many nations, antibiotic resistance is linked to overuse, abuse, and misuse of these drugs. The World Health Organization (WHO) recognized 12 families of bacteria that present the greatest harm to human health, where options of antibiotic therapy are extremely limited. Therefore, this paper reviews possible new ways for the development of novel classes of antibiotics for which there is no pre-existing resistance in human bacterial pathogens. By utilizing research and technology such as nanotechnology and computational methods (such as in silico and Fragment-based drug design (FBDD)), there has been an improvement in antimicrobial actions and selectivity with target sites. Moreover, there are antibiotic alternatives, such as antimicrobial peptides, essential oils, anti-Quorum sensing agents, darobactins, vitamin B6, bacteriophages, odilorhabdins, 18β-glycyrrhetinic acid, and cannabinoids. Additionally, drug repurposing (such as with ticagrelor, mitomycin C, auranofin, pentamidine, and zidovudine) and synthesis of novel antibacterial agents (including lactones, piperidinol, sugar-based bactericides, isoxazole, carbazole, pyrimidine, and pyrazole derivatives) represent novel approaches to treating infectious diseases. Nonetheless, prodrugs (e.g., siderophores) have recently shown to be an excellent platform to design a new generation of antimicrobial agents with better efficacy against multidrug-resistant bacteria. Ultimately, to combat resistant bacteria and to stop the spread of resistant illnesses, regulations and public education regarding the use of antibiotics in hospitals and the agricultural sector should be combined with research and technological advancements. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Antimicrobial Agents)

► Show Figures

Figure 1

28 pages, 8474 KiB

Open AccessFeature PaperReview

Fragment-Based Lead Discovery Strategies in Antimicrobial Drug Discovery

by Monika I. Konaklieva and Balbina J. Plotkin

Antibiotics 2023, 12(2), 315; https://doi.org/10.3390/antibiotics12020315 - 3 Feb 2023

Cited by 3 | Viewed by 2844

Abstract

Fragment-based lead discovery (FBLD) is a powerful application for developing ligands as modulators of disease targets. This approach strategy involves identification of interactions between low-molecular weight compounds (100–300 Da) and their putative targets, often with low affinity (K_D ~0.1–1 mM) interactions. The [...] Read more.

Fragment-based lead discovery (FBLD) is a powerful application for developing ligands as modulators of disease targets. This approach strategy involves identification of interactions between low-molecular weight compounds (100–300 Da) and their putative targets, often with low affinity (K_D ~0.1–1 mM) interactions. The focus of this screening methodology is to optimize and streamline identification of fragments with higher ligand efficiency (LE) than typical high-throughput screening. The focus of this review is on the last half decade of fragment-based drug discovery strategies that have been used for antimicrobial drug discovery. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Antimicrobial Agents)

► Show Figures

Figure 1

25 pages, 12348 KiB

Open AccessReview

Potential Nitrogen-Based Heterocyclic Compounds for Treating Infectious Diseases: A Literature Review

by Mohammad Aatif, Muhammad Asam Raza, Khadija Javed, Swah Mohd. Nashre-ul-Islam, Mohd Farhan and Mir Waqas Alam

Antibiotics 2022, 11(12), 1750; https://doi.org/10.3390/antibiotics11121750 - 3 Dec 2022

Cited by 52 | Viewed by 4598

Abstract

Heterocyclic compounds are considered as one of the major and most diverse family of organic compounds. Nowadays, the demand for these compounds is increasing day-by-day due to their enormous synthetic and biological applications. These heterocyclic compounds have unique antibacterial activity against various Gram-positive [...] Read more.

Heterocyclic compounds are considered as one of the major and most diverse family of organic compounds. Nowadays, the demand for these compounds is increasing day-by-day due to their enormous synthetic and biological applications. These heterocyclic compounds have unique antibacterial activity against various Gram-positive and Gram-negative bacterial strains. This review covers the antibacterial activity of different heterocyclic compounds with nitrogen moiety. Some of the derivatives of these compounds show excellent antibacterial activity, while others show reasonable activity against bacterial strains. This review paper aims to bring and discuss the detailed information on the antibacterial activity of various nitrogen-based heterocyclic compounds. It will be helpful for the future evolution of diseases to synthesize new and effective drug molecules. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Antimicrobial Agents)

► Show Figures

Figure 1

27 pages, 12654 KiB

Open AccessReview

Antimicrobial Activity of Lactones

by Marcelina Mazur and Dorota Masłowiec

Antibiotics 2022, 11(10), 1327; https://doi.org/10.3390/antibiotics11101327 - 29 Sep 2022

Cited by 20 | Viewed by 3355

Abstract

The development of bacterial resistance to antibiotics and the consequent lack of effective therapy is one of the biggest problems in modern medicine. A consequence of these processes is an urgent need to continuously design and develop novel antimicrobial agents. Among the compounds [...] Read more.

The development of bacterial resistance to antibiotics and the consequent lack of effective therapy is one of the biggest problems in modern medicine. A consequence of these processes is an urgent need to continuously design and develop novel antimicrobial agents. Among the compounds showing antimicrobial potential, lactones are a group to explore. For centuries, their antimicrobial activities have been used in folk medicine. Currently, novel lactone compounds are continuously described in the literature. Some of those structures exhibit high antimicrobial potential and some are an inspiration for design and synthesis of future drugs. This paper describes recent developments on antimicrobial lactones with smaller ring sizes, up to seven membered ε-lactones. Their isolation from natural sources, chemical synthesis, synergistic activity with antibiotics, and effects on quorum sensing are presented herein. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Antimicrobial Agents)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Design and Synthesis of Novel Antimicrobial Agents

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (12 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI