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...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2010-02, Vol.20 (3), p.1247-1251
Main Authors: Adsule, Shreelekha, Banerjee, Sanjeev, Ahmed, Fakhara, Padhye, Subhash, Sarkar, Fazlul H.
Format: Article
Language:English
Subjects:
Anticancer
Antineoplastic agents
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - chemistry
Antineoplastic Agents - toxicity
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - chemistry
Antineoplastic Combined Chemotherapy Protocols - toxicity
Apoptosis - drug effects
Apoptosis - physiology
Biological and medical sciences
Cell Line, Tumor
General aspects
Humans
Hybrid
Isothiocyanates
Isothiocyanates - administration & dosage
Isothiocyanates - chemistry
Isothiocyanates - toxicity
Medical sciences
Pharmacology. Drug treatments
Progesterone
Progesterone - administration & dosage
Progesterone - chemistry
Progesterone - toxicity
Recombinant Fusion Proteins - administration & dosage
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - toxicity
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Summary: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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2009.11.128