Design, Synthesis, and Molecular Docking Study of Novel Heterocycles Incorporating 1,3,4-Thiadiazole Moiety as Potential Antimicrobial and Anticancer Agents
Mohamed El-Naggar,
Hanan A. Sallam,
Safaa S. Shaban,
Salwa S. Abdel-Wahab,
Abd El-Galil E. Amr,
Mohammad E. Azab,
Eman S. Nossier,
Mohamed A. Al-Omar
Affiliations
Mohamed El-Naggar
Chemistry Department, Faculty of Sciences, University of Sharjah, Sharjah 27272, UAE
Hanan A. Sallam
Synthetic Organic Laboratory, Chemistry Department, Faculty of Science, Ain Shams University, Cairo 11566, Egypt
Safaa S. Shaban
Synthetic Organic Laboratory, Chemistry Department, Faculty of Science, Ain Shams University, Cairo 11566, Egypt
Salwa S. Abdel-Wahab
Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt, New Cairo 11835, Egypt
Abd El-Galil E. Amr
Pharmaceutical Chemistry Department, Drug Exploration and Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Mohammad E. Azab
Synthetic Organic Laboratory, Chemistry Department, Faculty of Science, Ain Shams University, Cairo 11566, Egypt
Pharmaceutical Chemistry Department, Drug Exploration and Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
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.
