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5-(Thiophen-2-yl)-1,3,4-thiadiazole derivatives: synthesis, molecular docking and in vitro cytotoxicity evaluation as potential anticancer agents

Authors Gomha SM, Edrees MM, Muhammad ZA, El-Reedy AA

Received 11 February 2018

Accepted for publication 29 March 2018

Published 30 May 2018 Volume 2018:12 Pages 1511—1523

DOI https://doi.org/10.2147/DDDT.S165276

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Tuo Deng


Sobhi M Gomha,1 Mastoura M Edrees,2,3 Zeinab A Muhammad,2 Ahmed AM El-Reedy4

1Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt; 2Department of Organic Chemistry, National Organization for Drug Control and Research (NODCAR), Giza, Egypt; 3Department of Chemistry, Faculty of Science, King Khalid University, Abha, Saudi Arabia; 4Department of Basic and Applied Science, Faculty of Oral and Dental Medicine, Nahda University, Beni-Suef, Egypt

Background: Nowadays, cancer is an important public health problem in all countries. Limitations of current chemotherapy for neoplastic diseases such as severe adverse reactions and tumor resistance to the chemotherapeutic drugs have been led to a temptation for focusing on the discovery and development of new compounds with potential anticancer activity. The importance of thiophene and thiadiazole rings as scaffolds present in a wide range of therapeutic agents has been well reported and has driven the synthesis of a large number of novel antitumor agents.
Methods: A series of new 1,3,4-thiadiazoles were synthesized by heterocyclization of N-(4-nitrophenyl)thiophene-2-carbohydrazonoyl chloride with a variety of hydrazine-carbodithioate derivatives. The mechanisms of these reactions were discussed and the structure of the new products was elucidated via spectral data and elemental analysis. All the new synthesized compounds were investigated for in vitro activities against human hepatocellular carcinoma (HepG-2) and human lung cancer (A-549) cell lines compared with cisplatin standard anticancer drug. Moreover, molecular docking using MOE 2014.09 software was also carried out for the high potent compound 20b with the binding site of dihydrofolate reductase (DHFR, PDB ID (3NU0)).
Results: The results showed that compound 20b has promising activities against HepG-2 and A-549 cell lines (IC50 value of 4.37±0.7 and 8.03±0.5 μM, respectively) and the results of molecular docking supported the biological activity with total binding energy equals -1.6 E (Kcal/mol).
Conclusion: Overall, we synthesized a new series of 1,3,4-thiadiazoles as potential antitumor agents against HepG-2 and A-549 cell lines.

Keywords: hydrazonoyl chlorides, hydrazine-carbodithioates, 1,3,4-thiadiazoles, molecular docking, anticancer activity

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