Hybrid anticancer agents: isothiocyanate-progesterone conjugates as chemotherapeutic agents and insights into their cytotoxicities.
New hybrid molecules of isothiocyanate and progesterone and their metal complexes were synthesized exhibiting promising anti-proliferative and pro-apoptotic activity against breast and prostate cancer cells. These metal complex compounds exploited an existing cellular transport pathway for delivery of cytotoxic isothiocyanate moiety across cell membrane resulting in the inhibition of cell viability and inducing apoptosis. The highest apoptotic action was shown by the copper complex, which was mediated through the inhibition of Akt signaling similar to the one shown by isothiocyanate compounds. Our results underscore the possible role of metal redox cycling, and thus it is likely will open newer avenues for further optimization for the synthesis of novel active compounds through appropriate isothiocyanate pharmacophores.
Adsule
Shreelekha
S
Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, 740 HWCRC Bldg, 4100 John R Street, Detroit, MI 48201, USA.
Banerjee
Sanjeev
S
Ahmed
Fakhara
F
Padhye
Subhash
S
Sarkar
Fazlul H
FH
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D017879:Isothiocyanates / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity*; D011374:Progesterone / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*
D000970:Antineoplastic Agents; D017879:Isothiocyanates; D011993:Recombinant Fusion Proteins; C037152:isothiocyanic acid; D011374:Progesterone