Isatin-β-thiocarbohydrazones: Microwave-assisted synthesis, antitumor activity and structure-activity relationship

Eur J Med Chem. 2017 Mar 10:128:36-44. doi: 10.1016/j.ejmech.2017.01.030.

Moustafa T Gabr ¹, Nadia S El-Gohary ², Eman R El-Bendary ³, Mohamed M El-Kerdawy ³, Nanting Ni ⁴

Affiliations

1 Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt; Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.
2 Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: dr.nadiaelgohary@yahoo.com.
3 Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
4 Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.

PMID: 28147307 DOI: 10.1016/j.ejmech.2017.01.030

Abstract

A new series of isatin-β-thiocarbohydrazones was synthesized based on the pharmacophoric features of triapine required for metal chelation. Our strategy involved the modifications of triapine basic skeleton by replacing pyridinyl moiety with isatin which retains the tridentate feature of triapine needed for metal chelation. The new compounds were esteemed for their antitumor efficacy against cervical Cancer (Hela) and kidney fibroblast Cancer (COS-7) cell lines. Compounds 4c, 4d, 5c and 5e exhibited remarkable efficacy against Hela cell line. In addition, compounds 4c, 4k, 4e, 5c and 5e displayed an outstanding efficacy against COS-7 cell line. Compounds 4c, 4k, 4e, 5c and 5e were examined for their in vivo antitumor efficacy against Ehrlich ascites carcinoma (EAC) in mice. Pharmacophore mapping was performed to study the structural features of the synthesized compounds compared to triapine and to identify the essential moieties required for potent and selective antitumor activity.

Keywords

3D pharmacophore elucidation; Antitumor activity; Isatin-β-thiocarbohydrazones; Synthesis.

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