A novel pregnene analogs: synthesis, cytotoxicity on prostate cancer of PC-3 and LNCPa-AI cells and in silico molecular docking study

New pregnene analogs of N -hydroxamic acid 6 , imino-propane hydrazides 7 and 8 as well as the aryl amides 9 – 11 , oxadiazole, pyrazole and sulfinyl analogs 13 – 15 , via the hydrazide analog 5 of methyl ((5-pregnen-3β,17β-diol-15α-yl)thio)propanoate ( 4 ) were synthesized. The in vitro cytotoxic activities of selected synthesized steroids against two human prostate cancer cell lines (PC-3, and LNCaP-AI) were evaluated by MTT assay. Compound 10 was the most active cytotoxic agent among these steroids against PC-3 and LNCaP-AI cell lines with inhibition of 96.2%, and 93.6% at concentration levels of 10.0 μM and 91.8%, and of 79.8% at concentration of 1.0 μM, respectively. Molecular docking study of 10 showed a hydrogen bonding with the amino acid Asn705 residue of the receptor 1E3G, together with hydrophobic interactions. Therefore, compound 10 can be considered as a promising anticancer agent due to its potent cytotoxic activity. Graphic abstract