Isatin-β-thiocarbohydrazones: Microwave-assisted synthesis, antitumor activity and structure-activity relationship.
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.
Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt; Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.
Moustafa T
MT
Gabr
Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: dr.nadiaelgohary@yahoo.com.
Nadia S
NS
El-Gohary
Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Eman R
ER
El-Bendary
Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Mohamed M
MM
El-Kerdawy
Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.
Nanting
N
Ni
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019556:COS Cells; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D006834:Hydrazines / Q000737:chemistry*; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007510:Isatin / Q000737:chemistry*; D008297:Male; D051379:Mice; D008872:Microwaves; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
C000616831:1-((2-chloro-6-fluorobenzylidene)amino)-3-((5-methyl-2-oxo-2,3-dihydro-1H-indol-3-ylidene)amino)thiourea; D000970:Antineoplastic Agents; D006834:Hydrazines; D007211:Indoles; C011368:thiocarbohydrazide; D007510:Isatin; D013890:Thiourea
3D pharmacophore elucidation; Antitumor activity; Isatin-β-thiocarbohydrazones; Synthesis