title: Development of new estradiol-cationic lipid hybrids: ten-carbon twin chain cationic lipid is a more suitable partner for estradiol to elicit better anticancer activity.
abstract: The present study illustrates the synthesis and anticancer evaluation of six, ten, twelve and fourteen carbon chain containing cationic lipidated-estradiol hybrids. Previously, we have established the lipidation strategy to introduce anticancer activities in various pharmacophores including estradiol (ES). In this structure activity study the length of the carbon chain is narrowed down between C6-C14 to screen out the most potent anticancer molecule among the class. Among the newly developed ES-cationic lipid conjugates, ten-carbon chain containing derivative, ES-C10 (5c) exhibited 4-12 folds better anticancer activity than the previously established derivative, ES-C8 (5b) in various cancer cells of different origin. Moreover cytotoxicity of this molecule was not observed in non-cancer cells. Notably, in spite of bearing estrogenic moiety, ES-C10 exhibited anticancer activity irrespective of estrogen receptor (ER) expression status. ES-C10 exhibited prominent sub-G0 arrest of cancer cells with concomitant induction of apoptosis and demonstrated significant inhibition of tumor growth in mouse melanoma model. Collectively, ES-C10 exemplifies the development of an anticancer agent with broader activity against cancer cells of different origins.
authors.affiliation: Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Hyderabad, Andhra Pradesh 500007, India.
authors.forename: Godeshala
authors.initials: G
authors.lastname: Sudhakar
authors.affiliation: Division of Natural Products Chemistry, CSIR- Indian Institute of Chemical Technology, Hyderabad, Andhra Pradesh 500007, India; Academy of Scientific and Innovative Research (AcSIR), 2 Rafi Marg, New Delhi 110 001, India. Electronic address: suriiict@hotmail.com.
authors.forename: Surendar Reddy
authors.initials: SR
authors.lastname: Bathula
authors.affiliation: Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Hyderabad, Andhra Pradesh 500007, India; Academy of Scientific and Innovative Research (AcSIR), 2 Rafi Marg, New Delhi 110 001, India. Electronic address: banerjee@iict.res.in.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Banerjee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016466:CHO Cells; D002412:Cations / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004958:Estradiol / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002412:Cations; D008055:Lipids; D004958:Estradiol
keywords: Anti cancer activity; Apoptosis; Cationic lipid derivatives; Estradiol; Hybrid molecules