Reaction of pregnenolone with cyanoacetylhydrazine: novel synthesis of hydrazide-hydrazone, pyrazole, pyridine, thiazole, thiophene derivatives and their cytotoxicity evaluations.
Pregnenolone (1) was used as a template to develop new anticancer compounds. Ring D modification of 1 through its reaction with cyanoacetylhydrazine (2) gave the hydrazide-hydrazone derivative 3. The latter compound underwent heterocyclization reactions to give the pyrazole, pyridine, thiazole and thiophene derivatives of pregnenolone. The cytotoxicity of the newly synthesized heterocyclic steroids against three human tumor cell lines namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) were studied. Some of tested compounds were found to exhibit much higher inhibitory effects towards the three tumor cell lines than the reference drug, doxorubicin.
Chemistry Department, Faculty of Science, Cairo University, Cario, Egypt. raafat_mohareb@yahoo.com
Rafat M
RM
Mohareb
Fatima
F
Al-Omran
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006834:Hydrazines / Q000737:chemistry*; D006835:Hydrazones / Q000138:chemical synthesis* / Q000494:pharmacology; D009570:Nitriles / Q000737:chemistry*; D011284:Pregnenolone / Q000737:chemistry*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology
D000970:Antineoplastic Agents; D006834:Hydrazines; D006835:Hydrazones; D009570:Nitriles; D011720:Pyrazoles; D011725:Pyridines; D013844:Thiazoles; D013876:Thiophenes; D011284:Pregnenolone; C014949:acetylhydrazine