Reddy, Doma Mahendhar and Qazi, Naveed A. and Sawant, Sanghpal D. and Bandey, Abid H. and Srinivas, Jada and Shankar, Mannepalli and Singh, Shashank K. and Verma, Monika and Chashoo, Gousia and Saxena, Arpita and Mondhe, Dilip and Saxena, Ajit K. and Sethi, V.K. and Taneja, Subhash C. and Qazi, Gulam N. and Sampath Kumar, H.M. (2011) Design and synthesis of spiro derivatives of parthenin as novel anti-cancer agents. European Journal of Medicinal Chemistry, 46 (8). pp. 3210-3217. ISSN 02235234

PDF - Published Version Restricted to Registered users only Download (675Kb) | Request a copy

Abstract

Several novel spiro derivatives of parthenin (1) have been synthesized by the dipolar cycloaddition using various dipoles viz; benzonitrile oxides, nitrones and azides with exocyclic double bond of C ring(a-methylene-g-butyrolactone). Majority of the compounds exhibited improved anti-cancer activity compared to the parthenin, when screened for their in vitro cytotoxicity against three human cancer cell lines viz., SW-620, DU-145 and PC-3. In vivo screening of select analog revealed improved anti-cancer activity with low mammalian toxicity as compared to parthenin. The results of the cytotoxicity pattern of these derivatives reveals the SAR of these sesquiterpinoid lactones and possible role of a,b-unsaturated ketone of parthenin in inhibiting NF-kB. A mechanistic correlation of anti-cancer activity along with in vivo and western blotting experiments has been described.

Item Type:	Article
Subjects:	Chemical Sciences
Divisions:	UNSPECIFIED
Depositing User:	Mr. Amit Nargotra
Date Deposited:	28 Dec 2011 08:25
Last Modified:	28 Dec 2011 08:25
URI:	http://iiim.csircentral.net/id/eprint/236

Actions (login required)

View Item