International Journal of Molecular Sciences

Editorial

Jump to: Research

7 pages, 217 KiB

Open AccessEditorial

Special Issue: “Rational Design and Synthesis of Bioactive Molecules”

by Irena Kostova

Int. J. Mol. Sci. 2024, 25(18), 9927; https://doi.org/10.3390/ijms25189927 - 14 Sep 2024

Viewed by 648

Abstract

The rational design of novel bioactive molecules is a critical but challenging task in drug discovery [...] Full article

(This article belongs to the Special Issue Rational Design and Synthesis of Bioactive Molecules)

Research

Jump to: Editorial

12 pages, 754 KiB

Open AccessArticle

Bioreduction of 4′-Hydroxychalcone in Deep Eutectic Solvents: Optimization and Efficacy with Various Yeast Strains

by Paweł Chlipała, Tomasz Janeczko and Marcelina Mazur

Int. J. Mol. Sci. 2024, 25(13), 7152; https://doi.org/10.3390/ijms25137152 - 28 Jun 2024

Cited by 4 | Viewed by 703

Abstract

4′-dihydrochalcones are secondary metabolites isolated from many medicinal plants and from the resin known as ‘dragon’s blood’. Due to their biological potential, our research objective was to determine the possibilities of using biocatalysis processes carried out in deep eutectic solvents (DESs) to obtain [...] Read more.

4′-dihydrochalcones are secondary metabolites isolated from many medicinal plants and from the resin known as ‘dragon’s blood’. Due to their biological potential, our research objective was to determine the possibilities of using biocatalysis processes carried out in deep eutectic solvents (DESs) to obtain 4′-dihydrochalcones as a model compound. The processes were carried out in a culture of the yeast Yarrowia lipolytica KCh 71 and also in cultures of strains of the genera Rhodotorula and Debaryomyces. Based on the experiments carried out, an optimum process temperature of 35 °C was chosen, and the most suitable DES contained glycerol as a hydrogen bond donor (HBD). For a medium with 30% water content (DES 11), the conversion observed after 24 h exceeded 70%, while increasing the amount of water to 50% resulted in a similar level of conversion after just 1 h. A fivefold increase in the amount of added substrate resulted in a reduction in conversion, which reached 30.3%. Of the other yeast strains tested, Rhodotorula marina KCh 77 and Rhodotorula rubra KCh 4 also proved to be good biocatalysts for the bioreduction process. For these strains, the conversion reached 95.4% and 95.1%, respectively. These findings highlight the potential of yeast as a biocatalyst for the selective reduction of α,β-unsaturated ketones and the possibility of using a DESs as a reaction medium in this process. Full article

(This article belongs to the Special Issue Rational Design and Synthesis of Bioactive Molecules)

► Show Figures

Figure 1

13 pages, 5791 KiB

Open AccessArticle

Design and Synthesis of Pleuromutilin Derivatives as Antibacterial Agents Using Quantitative Structure–Activity Relationship Model

by Jiaming Zhang, Qinqin Liu, Haoxia Zhao, Guiyu Li, Yunpeng Yi and Ruofeng Shang

Int. J. Mol. Sci. 2024, 25(4), 2256; https://doi.org/10.3390/ijms25042256 - 13 Feb 2024

Cited by 1 | Viewed by 1254

Abstract

The quantitative structure–activity relationship (QSAR) is one of the most popular methods for the virtual screening of new drug leads and optimization. Herein, we collected a dataset of 955 MIC values of pleuromutilin derivatives to construct a 2D-QSAR model with an accuracy of [...] Read more.

The quantitative structure–activity relationship (QSAR) is one of the most popular methods for the virtual screening of new drug leads and optimization. Herein, we collected a dataset of 955 MIC values of pleuromutilin derivatives to construct a 2D-QSAR model with an accuracy of 80% and a 3D-QSAR model with a non-cross-validated correlation coefficient (r²) of 0.9836 and a cross-validated correlation coefficient (q²) of 0.7986. Based on the obtained QSAR models, we designed and synthesized pleuromutilin compounds 1 and 2 with thiol-functionalized side chains. Compound 1 displayed the highest antimicrobial activity against both Staphylococcus aureus ATCC 29213 (S. aureus) and Methicillin-resistant Staphylococcus aureus (MRSA), with minimum inhibitory concentrations (MICs) < 0.0625 μg/mL. These experimental results confirmed that the 2D and 3D-QSAR models displayed a high accuracy of the prediction function for the discovery of lead compounds from pleuromutilin derivatives. Full article

(This article belongs to the Special Issue Rational Design and Synthesis of Bioactive Molecules)

► Show Figures

Figure 1

22 pages, 2834 KiB

Open AccessArticle

Cyclobutanone Inhibitors of Diaminopimelate Desuccinylase (DapE) as Potential New Antibiotics

by Thahani S. Habeeb Mohammad, Emma H. Kelley, Cory T. Reidl, Katherine Konczak, Megan Beulke, Janielle Javier, Kenneth W. Olsen and Daniel P. Becker

Int. J. Mol. Sci. 2024, 25(2), 1339; https://doi.org/10.3390/ijms25021339 - 22 Jan 2024

Cited by 1 | Viewed by 1324

Abstract

Based on our previous success in using cyclobutanone derivatives as enzyme inhibitors, we have designed and prepared a 37-member library of α-aminocyclobutanone amides and sulfonamides, screened for inhibition of the bacterial enzyme diaminopimelate desuccinylase (DapE), which is a promising antibiotic target, and identified [...] Read more.

Based on our previous success in using cyclobutanone derivatives as enzyme inhibitors, we have designed and prepared a 37-member library of α-aminocyclobutanone amides and sulfonamides, screened for inhibition of the bacterial enzyme diaminopimelate desuccinylase (DapE), which is a promising antibiotic target, and identified several inhibitors with micromolar inhibitory potency. Molecular docking suggests binding of the deprotonated hydrate of the strained cyclobutanone, and thermal shift analysis with the most potent inhibitor (3y, IC₅₀ = 23.1 µM) enabled determination of a K_i value of 10.2 +/− 0.26 µM and observed two separate T_m values for H. influenzae DapE (HiDapE). Full article

(This article belongs to the Special Issue Rational Design and Synthesis of Bioactive Molecules)

► Show Figures

Figure 1

16 pages, 4835 KiB

Open AccessArticle

Identification of a Pentasaccharide Lead Compound with High Affinity to the SARS-CoV-2 Spike Protein via In Silico Screening

by Binjie Li, Tianji Zhang, Hui Cao, Vito Ferro, Jinping Li and Mingjia Yu

Int. J. Mol. Sci. 2023, 24(22), 16115; https://doi.org/10.3390/ijms242216115 - 9 Nov 2023

Cited by 1 | Viewed by 1377

Abstract

The spike (S) protein on the surface of the SARS-CoV-2 virus is critical to mediate fusion with the host cell membrane through interaction with angiotensin-converting enzyme 2 (ACE2). Additionally, heparan sulfate (HS) on the host cell surface acts as an attachment factor to [...] Read more.

The spike (S) protein on the surface of the SARS-CoV-2 virus is critical to mediate fusion with the host cell membrane through interaction with angiotensin-converting enzyme 2 (ACE2). Additionally, heparan sulfate (HS) on the host cell surface acts as an attachment factor to facilitate the binding of the S receptor binding domain (RBD) to the ACE2 receptor. Aiming at interfering with the HS-RBD interaction to protect against SARS-CoV-2 infection, we have established a pentasaccharide library composed of 14,112 compounds covering the possible sulfate substitutions on the three sugar units (GlcA, IdoA, and GlcN) of HS. The library was used for virtual screening against RBD domains of SARS-CoV-2. Molecular modeling was carried out to evaluate the potential antiviral properties of the top-hit pentasaccharide focusing on the interactive regions around the interface of RBD-HS-ACE2. The lead pentasaccharide with the highest affinity for RBD was analyzed via drug-likeness calculations, showing better predicted druggable profiles than those currently reported for RBD-binding HS mimetics. The results provide significant information for the development of HS-mimetics as anti-SARS-CoV-2 agents. Full article

(This article belongs to the Special Issue Rational Design and Synthesis of Bioactive Molecules)

► Show Figures

Figure 1

17 pages, 5235 KiB

Open AccessArticle

The Effect of Polymer Blends on the In Vitro Release/Degradation and Pharmacokinetics of Moxidectin-Loaded PLGA Microspheres

by Hongjuan Zhang, Zhen Yang, Di Wu, Baocheng Hao, Yu Liu, Xuehong Wang, Wanxia Pu, Yunpeng Yi, Ruofeng Shang and Shengyi Wang

Int. J. Mol. Sci. 2023, 24(19), 14729; https://doi.org/10.3390/ijms241914729 - 29 Sep 2023

Cited by 4 | Viewed by 1511

Abstract

To investigate the effect of polymer blends on the in vitro release/degradation and pharmacokinetics of moxidectin-loaded PLGA microspheres (MOX-MS), four formulations (F1, F2, F3 and F4) were prepared using the O/W emulsion solvent evaporation method by blending high (75/25, 75 kDa) and low [...] Read more.

To investigate the effect of polymer blends on the in vitro release/degradation and pharmacokinetics of moxidectin-loaded PLGA microspheres (MOX-MS), four formulations (F1, F2, F3 and F4) were prepared using the O/W emulsion solvent evaporation method by blending high (75/25, 75 kDa) and low (50/50, 23 kDa) molecular weight PLGA with different ratios. The addition of low-molecular-weight PLGA did not change the release mechanism of microspheres, but sped up the drug release of microspheres and drastically shortened the lag phase. The in vitro degradation results show that the release of microspheres consisted of a combination of pore diffusion and erosion, and especially autocatalysis played an important role in this process. Furthermore, an accelerated release method was also developed to reduce the period for drug release testing within one month. The pharmacokinetic results demonstrated that MOX-MS could be released for at least 60 days with only a slight blood drug concentration fluctuation. In particular, F3 displayed the highest AUC and plasma concentration (AUC_0–t = 596.53 ng/mL·d, C_{ave (day 30-day 60)} = 8.84 ng/mL), making it the optimal formulation. Overall, these results indicate that using polymer blends could easily adjust hydrophobic drug release from microspheres and notably reduce the lag phase of microspheres. Full article

(This article belongs to the Special Issue Rational Design and Synthesis of Bioactive Molecules)

► Show Figures

Figure 1

23 pages, 37842 KiB

Open AccessArticle

Peculiarities of the Spatial and Electronic Structure of 2-Aryl-1,2,3-Triazol-5-Carboxylic Acids and Their Salts on the Basis of Spectral Studies and DFT Calculations

by Mauricio Alcolea Palafox, Nataliya P. Belskaya and Irena P. Kostova

Int. J. Mol. Sci. 2023, 24(18), 14001; https://doi.org/10.3390/ijms241814001 - 12 Sep 2023

Cited by 3 | Viewed by 995

Abstract

The molecular structure and vibrational spectra of six 1,2,3-triazoles-containing molecules with possible anticancer activity were investigated. For two of them, the optimized geometry was determined in the monomer, cyclic dimer and stacking forms using the B3LYP, M06-2X and MP2 methods implemented in the [...] Read more.

The molecular structure and vibrational spectra of six 1,2,3-triazoles-containing molecules with possible anticancer activity were investigated. For two of them, the optimized geometry was determined in the monomer, cyclic dimer and stacking forms using the B3LYP, M06-2X and MP2 methods implemented in the GAUSSIAN-16 program package. The effect of the para-substitution on the aryl ring was evaluated based on changes in the molecular structure and atomic charge distribution of the triazole ring. An increment in the positive N₄ charge was linearly related to a decrease in both the aryl ring and the carboxylic group rotation, with respect to the triazole ring, and by contrast, to an increment in the pyrrolidine ring rotation. Anionic formation had a larger effect on the triazole ring structure than the electronic nature of the different substituents on the aryl ring. Several relationships were obtained that could facilitate the selection of substituents on the triazole ring for their further synthesis. The observed IR and Raman bands in the solid state of two of these compounds were accurately assigned according to monomer and dimer form calculations, together with the polynomic scaling equation procedure (PSE). The large red-shift of the C=O stretching mode indicates that strong H-bonds in the dimer form appear in the solid state through this group. Full article

(This article belongs to the Special Issue Rational Design and Synthesis of Bioactive Molecules)

► Show Figures

Figure 1

14 pages, 1683 KiB

Open AccessArticle

Antioxidant Properties of Selected Flavonoids in Binary Mixtures—Considerations on Myricetin, Kaempferol and Quercetin

by Małgorzata Olszowy-Tomczyk and Dorota Wianowska

Int. J. Mol. Sci. 2023, 24(12), 10070; https://doi.org/10.3390/ijms241210070 - 13 Jun 2023

Cited by 13 | Viewed by 1734

Abstract

Flavonoids, secondary plant metabolites with many health-promoting properties, including antioxidant, are a valuable component of food products, especially functional foods. In the latter, plant extracts are commonly used, the properties of which are attributed to the characteristic main ingredients. However, in a mixture [...] Read more.

Flavonoids, secondary plant metabolites with many health-promoting properties, including antioxidant, are a valuable component of food products, especially functional foods. In the latter, plant extracts are commonly used, the properties of which are attributed to the characteristic main ingredients. However, in a mixture the antioxidant properties of the individual ingredients do not always show an additive effect. This paper presents and discusses the antioxidant properties of naturally occurring flavonoid aglycones and their binary mixtures. In the experiments, model systems were used that differed in the volume of the alcoholic antioxidant solution in the measuring system and its concentration in the range in which it occurs in nature. Antioxidant properties were determined by ABTS and DPPH methods. The presented data proved that the dominant resultant effect in the mixtures is antioxidant antagonism. The magnitude of the observed antagonism depends on the mutual relations of individual components, their concentrations and the method used to assess antioxidant properties. It was shown that the observed non-additive antioxidant effect of the mixture results from the formation of intramolecular hydrogen bonds between phenolic groups of the antioxidant molecule. The presented results may be useful in the context of proper design of functional foods. Full article

(This article belongs to the Special Issue Rational Design and Synthesis of Bioactive Molecules)

► Show Figures

Figure 1

19 pages, 6298 KiB

Open AccessArticle

Combined NMR Spectroscopy and Quantum-Chemical Calculations in Fluorescent 1,2,3-Triazole-4-carboxylic Acids Fine Structures Analysis

by Nikita E. Safronov, Irena P. Kostova, Mauricio Alcolea Palafox and Nataliya P. Belskaya

Int. J. Mol. Sci. 2023, 24(10), 8947; https://doi.org/10.3390/ijms24108947 - 18 May 2023

Cited by 10 | Viewed by 1642

Abstract

The peculiarities of the optical properties of 2-aryl-1,2,3-triazole acids and their sodium salts were investigated in different solvents (1,4-dioxane, dimethyl sulfoxide DMSO, methanol MeOH) and in mixtures with water. The results were discussed in terms of the molecular structure formed by inter- and [...] Read more.

The peculiarities of the optical properties of 2-aryl-1,2,3-triazole acids and their sodium salts were investigated in different solvents (1,4-dioxane, dimethyl sulfoxide DMSO, methanol MeOH) and in mixtures with water. The results were discussed in terms of the molecular structure formed by inter- and intramolecular noncovalent interactions (NCIs) and their ability to ionize in anions. Theoretical calculations using the Time-Dependent Density Functional Theory (TDDFT) were carried out in different solvents to support the results. In polar and nonpolar solvents (DMSO, 1,4-dioxane), fluorescence was provided by strong neutral associates. Protic MeOH can weaken the acid molecules’ association, forming other fluorescent species. The fluorescent species in water exhibited similar optical characteristics to those of triazole salts; therefore, their anionic character can be assumed. Experimental ¹H and ¹³C-NMR spectra were compared to their corresponding calculated spectra using the Gauge-Independent Atomic Orbital (GIAO) method and several relationships were established. All these findings showed that the obtained photophysical properties of the 2-aryl-1,2,3-triazole acids noticeably depend on the environment and, therefore, are good candidates as sensors for the identification of analytes with labile protons. Full article

(This article belongs to the Special Issue Rational Design and Synthesis of Bioactive Molecules)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Rational Design and Synthesis of Bioactive Molecules

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Related Special Issue

Published Papers (9 papers)

Editorial

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI