Novel dimeric Smac analogs as prospective anticancer agents |
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Institution: | 1. Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan 62102, Republic of China |
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Abstract: | A small library of monovalent Smac mimics with general structure NMeAla-Tle-(4R)-4-Benzyl-Pro-Xaa-cysteamide, was synthesized (Xaa = hydrophobic residue). The library was screened in vitro against human breast cancer cell lines MCF-7 and MDA-MB-231, and two most active compounds oligomerized via S-alkylation giving bivalent and trivalent derivatives. The most active bivalent analogue SMAC17-2X was tested in vivo and in physiological conditions (mouse model) it exerted a potent anticancer effect resulting in ∼23.4 days of tumor growth delay at 7.5 mg/kg dose. Collectively, our findings suggest that bivalent Smac analogs obtained via S-alkylation protocol may be a suitable platform for the development of new anticancer therapeutics. |
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Keywords: | Smac mimics New anticancer agents Peptides S-alkylation of peptides Apoptosis |
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