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- Tran, Xuan-Truc Dinh, et al.
(författare)
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Integration of the Butina algorithm and ensemble learning strategies for the advancement of a pharmacophore ligand-based model : an in silico investigation of apelin agonists
- 2024
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Ingår i: Frontiers in Chemistry. - : Frontiers Media S.A.. - 2296-2646. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: 3D pharmacophore models describe the ligand's chemical interactions in their bioactive conformation. They offer a simple but sophisticated approach to decipher the chemically encoded ligand information, making them a valuable tool in drug design.Methods: Our research summarized the key studies for applying 3D pharmacophore models in virtual screening for 6,944 compounds of APJ receptor agonists. Recent advances in clustering algorithms and ensemble methods have enabled classical pharmacophore modeling to evolve into more flexible and knowledge-driven techniques. Butina clustering categorizes molecules based on their structural similarity (indicated by the Tanimoto coefficient) to create a structurally diverse training dataset. The learning method combines various individual pharmacophore models into a set of pharmacophore models for pharmacophore space optimization in virtual screening.Results: This approach was evaluated on Apelin datasets and afforded good screening performance, as proven by Receiver Operating Characteristic (AUC score of 0.994 ± 0.007), enrichment factor of (EF1% of 50.07 ± 0.211), Güner-Henry score of 0.956 ± 0.015, and F-measure of 0.911 ± 0.031.Discussion: Although one of the high-scoring models achieved statistically superior results in each dataset (AUC of 0.82; an EF1% of 19.466; GH of 0.131 and F1-score of 0.071), the ensemble learning method including voting and stacking method balanced the shortcomings of each model and passed with close performance measures.
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| 2. |
- Pham, Em Canh, et al.
(författare)
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N,2,6-Trisubstituted 1H-benzimidazole derivatives as a new scaffold of antimicrobial and anticancer agents : design, synthesis, in vitro evaluation, and in silico studies
- 2023
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Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 13:1, s. 399-420
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Tidskriftsartikel (refereegranskat)abstract
- Compounds containing benzimidazole moiety occupy privileged chemical space for discovering new bioactive substances. In continuation of our recent work, 69 benzimidazole derivatives were designed and synthesized with good to excellent yields of 46-99% using efficient synthesis protocol i.e. sodium metabisulfite catalyzed condensation of aromatic aldehydes with o-phenylenediamines to form 2-arylbenzimidazole derivatives followed by N-alkylation by conventional heating or microwave irradiation for diversification. Potent antibacterial compounds against MSSA and MRSA were discovered such as benzimidazole compounds 3k (2-(4-nitrophenyl), N-benzyl), 3l (2-(4-chlorophenyl), N-(4-chlorobenzyl)), 4c (2-(4-chlorophenyl), 6-methyl, N-benzyl), 4g (2-(4-nitrophenyl), 6-methyl, N-benzyl), and 4j (2-(4-nitrophenyl), 6-methyl, N-(4-chlorobenzyl)) with MIC of 4-16 mu g mL(-1). In addition, compound 4c showed good antimicrobial activities (MIC = 16 mu g mL(-1)) against the bacteria strains Escherichia coli and Streptococcus faecalis. Moreover, compounds 3k, 3l, 4c, 4g, and 4j have been found to kill HepG2, MDA-MB-231, MCF7, RMS, and C26 cancer cells with low mu M IC50 (2.39-10.95). These compounds showed comparable drug-like properties as ciprofloxacin, fluconazole, and paclitaxel in computational ADMET profiling. Finally, docking studies were used to assess potential protein targets responsible for their biological activities. Especially, we found that DHFR is a promising target both in silico and in vitro with compound 4c having IC50 of 2.35 mu M.
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| 3. |
- Pham, Em Canh, et al.
(författare)
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Synthesis of a Series of Novel 2-Amino-5-substituted 1,3,4-oxadiazole and 1,3,4-thiadiazole Derivatives as Potential Anticancer, Antifungal and Antibacterial Agents
- 2022
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Ingår i: Medicinal chemistry. - : Bentham Science Publishers Ltd.. - 1573-4064. ; 18:5, s. 558-573
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many compounds containing a five-membered heterocyclic ring display exceptional chemical properties and versatile biological activities. Objective: The objective of the present study was to prepare the 5-substituted 2-amino-1,3,4-oxadiazole and 2-amino-1,3,4-thiadiazole derivatives and evaluate their potential anticancer, antibacterial and antifungal activities. Methods: Twenty-seven derivatives were synthesized by iodine-mediated cyclization of semicarbazones or thiosemicarbazones obtained from condensation of semicarbazide or thiosemicarbazide and aldehydes. The structures were confirmed by H-1-NMR, C-13-NMR and MS spectra. The antibacterial and antifungal activities were evaluated by diffusion method and the anticancer activities were evaluated by MTT assay. Results: Twenty-seven derivatives have been synthesized in moderate to good yields. A number of derivatives exhibited potential antibacterial, antifungal and anticancer activities. Conclusion: Compounds (1b, 1e and 1g) showed antibacterial activity against Streptococcus faecalis, MSSA and MRSA with MC value ranging between 4 to 64 mu g/mL. Compound (2g) showed antifungal activity against Candida albicans (8 mu g/mL) and Aspergillus niger (64 mu g/mL). Compound (lo) exhibited high cytotoxic activity against HepG2 cell line (IC50 value 8.6 mu M) which is comparable to the activity of paclitaxel, and is non-toxic on LLC-PK1 normal cell line. The structure activity relationship and molecular docking study of the synthesized compounds have also been reported.
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