title: Design and synthesis of spiro derivatives of parthenin as novel anti-cancer agents.
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 (α-methylene-γ-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 α,β-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.
authors.affiliation: Synthetic and Biological Chemistry, Indian Institute of Integrative Medicine, Jammu 180001, India.
authors.forename: Doma Mahendhar
authors.initials: DM
authors.lastname: Reddy
authors.forename: Naveed A
authors.initials: NA
authors.lastname: Qazi
authors.forename: Sanghpal D
authors.initials: SD
authors.lastname: Sawant
authors.forename: Abid H
authors.initials: AH
authors.lastname: Bandey
authors.forename: Jada
authors.initials: J
authors.lastname: Srinivas
authors.forename: Mannepalli
authors.initials: M
authors.lastname: Shankar
authors.forename: Shashank K
authors.initials: SK
authors.lastname: Singh
authors.forename: Monika
authors.initials: M
authors.lastname: Verma
authors.forename: Gousia
authors.initials: G
authors.lastname: Chashoo
authors.forename: Arpita
authors.initials: A
authors.lastname: Saxena
authors.forename: Dilip
authors.initials: D
authors.lastname: Mondhe
authors.forename: Ajit K
authors.initials: AK
authors.lastname: Saxena
authors.forename: V K
authors.initials: VK
authors.lastname: Sethi
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Taneja
authors.forename: Gulam N
authors.initials: GN
authors.lastname: Qazi
authors.forename: H M
authors.initials: HM
authors.lastname: Sampath Kumar
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015153:Blotting, Western; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D053938:DNA Fragmentation / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009368:Neoplasm Transplantation; D009570:Nitriles / Q000737:chemistry; D010087:Oxides / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000494:pharmacology; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D009570:Nitriles; D010087:Oxides; D012717:Sesquiterpenes; D013141:Spiro Compounds; C014096:alpha-methylene gamma-butyrolactone; C022097:parthenin; C014356:benzonitrile; D015107:4-Butyrolactone