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 mu M, in comparison with Methotrexate (IC50 = 0.14 +/- 1.38 mu M). The highly potent DHFR inhibitors shared a similar molecular docking mode and made a critical hydrogen bond and arenearene interactions via Ser59 and Phe31 amino acid residues, respectively.