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

Autor:	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
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	1 3 4-thiadiazole antimicrobial anticancer dihydrofolate reductase molecular docking Organic chemistry QD241-441
Zdroj:	Molecules, Vol 24, Iss 6, p 1066 (2019)
Druh dokumentu:	article
ISSN:	1420-3049
DOI:	10.3390/molecules24061066
Popis:	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.
Databáze:	Directory of Open Access Journals
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