Design, Synthesis, and Molecular Docking Study of Novel Heterocycles Incorporating 1,3,4-Thiadiazole Moiety as Potential Antimicrobial and Anticancer Agents

Abstract

A new series of 5-(3,5-dinitrophenyl)-1,3,4-thiadiazole derivatives were prepared and evaluated for their in vitro antimicrobial, antitumor, and DHFR inhibition activity. Compounds 9, 10, 13, and 16 showed strong and broad-spectrum antimicrobial activity comparable to Amoxicillin and Fluconazole as positive antibiotic and antifungal controls, respectively. Compounds 6, 14, and 15 exhibited antitumor activity against four human cancer cell lines, CCRF-CEM leukemia, HCT-15 colon, PC-3 prostate, and UACC-257 melanoma cell lines using Doxorubicin as a reference drug. Compounds 10, 13, 14, and 15 proved to be the most active DHFR inhibitors with an IC50 range of 0.04 ± 0.82–1.00 ± 0.85 µM, in comparison with Methotrexate (IC50 = 0.14 ± 1.38 µM). The highly potent DHFR inhibitors shared a similar molecular docking mode and made a critical hydrogen bond and arene‒arene interactions via Ser59 and Phe31 amino acid residues, respectively.

Cytotoxic Properties of 1,3,4-Thiadiazole Derivatives—A Review

“…Doxorubicin was used as a reference drug. The compounds were characterized by selectivity of action against tumor cells [ 57 ].…”

Novel heterocyclic hybrids of pyrazole targeting dihydrofolate reductase: design, biological evaluation and in silico studies

“…The newly synthesised active targets 3a, 3b, 6a, 6b, 8a and 9a were assessed for their in vitro inhibition against dihydrofolate reductase (DHFR) in confirmatory diagnostic unit, Vacsera, Egypt. Methotrexate was used as a reference drug following the previously mentioned method 36 . The obtained results are depicted as IC 50 values of enzyme inhibition in Table 2.…”

Synthesis and Antimicrobial Studies of New [Tetrakis (1, 2, 4-Triazole / 1, 3, 4-Oxadiazole / 1, 3, 4-Thiadiazole] [Bis-(Benzene-1, 3, 5-Triyl)] Dioxymethylene Compounds

“…Recently, 4-amino-5-(3,5-dimethoxyphenyl)-4H- [1,2,4]triazole-3-thiol compound was prepared from the reaction 3,5-dimethoxy benzoic acid and thiocarbohydrazide in presence of sodium bicarbonate [22]. More recently and for the current year, a new series of [5-(3,5-dinitrophenyl)-1,3,4-thiadiazole] derivatives were prepared by different methods and evaluated for their antimicrobial and antitumor inhibition activity [23]. Otherwise, the other latterly new derivatives of 1,3,4-oxadiazole bearing sulfonamide were synthesized via [5-(5-cyclohexyl-1,3,4-oxadiazol-2-yl)-2-methyl-benzenesulfonyl chloride] and screened for their biological activities [24].…”