Efficient synthesis of novel 2-deoxy-C-nucleosides containing oxa and thiadiazole derivatives and their biological activity

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Compounds with a 1,2,4–triazole scaffold serve an essential role in organic synthesis, particularly in the synthesis of bioactive organic compounds; thus, the development of new approaches for modifying this scaffold is a very interesting framework of this study. To contribute to the development of an efficient method for the conversion of anticancer triazoles, a novel series of benzimidazole based 1,2,4‐triazoles was designed and synthesized. All the newly synthesized derivatives were characterized by NMR (1H &13C), FT–IR and mass spectrometry. Among the tested compounds, hybrids 5 b, 5 g exhibited exceptional anticancer susceptibilities with IC50=8.8±0.9, 9.2±1.5 μM against the tested HCA‐7cancer cell line. Anticancer profiles showed that compounds 5 d, 5 i had better anticancer inhibitory potency against a breast cancer cell line MCF‐7with IC50values 8.3±2.1, 10.6±1.2 μM, whereas 5 d, and 5 g showed potent anticancer activity against colorectal cancer cell line HT29 with IC50 values 7.1±±0.9, 7.7±1.2 μM respectively. From docking results, 5 d demonstrated highly stable binding amino acids LeuA : 2247, GlyA : 2449, SerA : 2409, HisA : 2379, AspA : 2373, LysA : 2318, IleA : 2317, IleA : 2246, IleA : 2412, AlaA : 2410, GlnA : 2452, AsnA : 2245, TyrA : 2243, and HisA : 2448, which play a crucial role enabling optimal ligand binding in a crystal structure tyrosine phosphatase mutated in colorectal cancer (PDB: 1WCH). Furthermore, the physicochemical and absorption, distribution, metabolism, and excretion (ADME) filtration molecular properties, estimation of bioactivity, and toxicity scores of these scaffolds were evaluated.

Synthesis of Benzimidazole Based 1,2,4‐Triazole Derivatives as Potential Anticancer Agents: In Silico Techniques

Chandrakar,

Sureddy,

Chedupaka

et al. 2024

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Design, Synthesis, in Vitro, and in Silico Evaluations of 1,3,4‐Oxadiazole Derivatives Linked to the Pyrrolo[2,3‐d]pyrimidine Moieties as Potent Antimicrobial Targets

Lal Patel,

Kumar Sureddy,

Boddupalli

et al. 2024

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Abstract1,3,4‐Oxadiazole and its derivatives are well known assorted motif in drug design and development. The development of bacterial infection drug resistance serves as justification for the discovery of novel antimicrobial drugs. Thus, a novel series of 1,3,4‐oxadiazole derivatives linked to pyrrolo[2,3‐d]pyrimidine 6 a–f and 7 a–e was designed, synthesized and fully characterized by 1H‐NMR, 13C‐NMR, FT‐IR and mass spectroscopic analysis. All of the compounds′ in‐vitro antibacterial and antifungal activities were reported, and final oxadiazoles 6 d, 6 e, 6 f, and 7 e showed excellent antimicrobial inhibitory activity as compared to standard drugs. The compounds 6 f and 7 a exhibited potent antifungal activity as a potent inhibitor against C. albicans with MICs 4.0±0.03, 7.5±0.02 μg/mL respectively. In order to determine the different binding interactions that the most active oxadiazoles had with the Staphylococcus aureus DHFR enzyme, a docking study was conducted. The results indicated that the residues of amino acid Thr96(X), Leu62(X), Arg44(X), Asn18(X), Glu17(X), Lys45(X), Thr121(X), Gln95(X), Asp120(X), Ser64(X), Gly94(X), and Phe16(X) had promising energy value, within the range of −6.84 to −9.63 kcal/mol (PDB: 3FRA). The most effective inhibitors, 6 and 7, also underwent in silico ADMET tests to predict their pharmacokinetic and physicochemical characteristics.

New Quinazolinone‐Tethered 1,2,3‐Triazoles aSs Potent Antimicrobial Agents: Design, Synthesis, Biological Evaluation and in silico Docking Study

Patel,

Sureddy,

Chedupaka

et al. 2024

Novel 1,2,3‐triazole acetamide linked quinazolinone derivatives were synthesized via click reaction, by reacting of 3‐methyl‐2‐(prop‐2‐yn‐1‐ylthio)quinazolin‐4(3H)‐one with various aryl azides as prominent fungal pathogen Candida albicans interactions. The prepared triazole compounds were characterized using mass spectrometry, 1H NMR, 13C NMR, and IR spectroscopic techniques. Compounds were screened for their in vitro antibacterial and antifungal activity against a variety of microorganisms namely, Bacillus subtilis, Enterococcus faecalis, Klebsiella pneumonia, Escherichia coli, Aspergillus fumigatus, Candida albicans, and Aspergillus clavatus. Quinazolinone linked p‐hydroxyphenyl, o, p‐dihydroxyphenyl and o‐dimethylamino phenyl triazoles showed a remarkable antibacterial activity against E. faecalis with MIC values of 3.20±0.01, 4.01±0.04, and 4.10±0.01 μg mL−1, and screened compounds p‐nitrophenyl substituted triazole, and p‐methylphenyl substituted triazole displayed a significant antifungal activity against C. albicans with MICs of 3.16±0.01, 4.06±0.03 μg mL−1, compared to itraconazole (MIC=3.32±0.02 μg mL−1). For further exploration of the anti‐fungal mechanism of action, molecular docking was carried out for these compounds in C. albicans active site as one of the important antifungal inhibitors (PDB: 1A19). Furthermore, the ADMET profile was evaluated for all the final triazole compounds in contrast to reference drugs moxifloxacin and itraconazole. In conclusion, we discovered a novel quinazolinone linked 1,2,3‐triazoles with promising antimicrobial activity and a favorable pharmacokinetic profile.