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.
Highlights
Dihydrofolate reductase (DHFR) is a prevalent enzyme that is present in all prokaryotic and eukaryotic cells
Molecules 2019, 24, 1066it was noticed that 1,3,4-thiadiazole derivatives possess many pharmacological literature survey, activities, such as antimicrobial, anti-hepatitis B viral, antitubercular, antileishmanial, analgesic, anti-inflammatory, anticancer, anticonvulsant, central nervous system (CNS) depressant, anti-inflammatory, anticancer, anticonvulsant, central nervous system (CNS) depressant, antioxidant, antioxidant, molluscicidal, antidiabetic, diuretic, and antihypertensive activities [9,10,11,12,13,14,15,16,17,18]
All synthesized compounds were examined for their in vitro antimicrobial, antitumor, and Dihydrofolate Reductase (DHFR) inhibition activity
Summary
Dihydrofolate reductase (DHFR) is a prevalent enzyme that is present in all prokaryotic and eukaryotic cells. It has a key role in folate metabolism and subsequently DNA and RNA synthesis [1,2]. 24, 1066it was noticed that 1,3,4-thiadiazole derivatives possess many pharmacological literature survey, activities, such as antimicrobial, anti-hepatitis B viral, antitubercular, antileishmanial, analgesic, anti-inflammatory, anticancer, anticonvulsant, central nervous system (CNS) depressant, anti-inflammatory, anticancer, anticonvulsant, central nervous system (CNS) depressant, antioxidant, antioxidant, molluscicidal, antidiabetic, diuretic, and antihypertensive activities [9,10,11,12,13,14,15,16,17,18].
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