Design and synthesis of spiro derivatives of parthenin as novel anti-cancer agents
| Autor: | Dilip M. Mondhe, Naveed A. Qazi, Gousia Chashoo, Doma Mahendhar Reddy, Subhash C. Taneja, Shashank K. Singh, Ajit Kumar Saxena, Jada Srinivas, Abid H. Bandey, Mannepalli Shankar, Sanghpal D. Sawant, H. M. Sampath Kumar, Vijay Kumar Sethi, Monika Verma, Gulam Nabi Qazi, A. K. Saxena |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Ketone Stereochemistry Blotting Western Antineoplastic Agents DNA Fragmentation Chemical synthesis chemistry.chemical_compound Mice Structure-Activity Relationship 4-Butyrolactone In vivo Cell Line Tumor Drug Discovery Nitriles Animals Humans Spiro Compounds Cytotoxicity Carcinoma Ehrlich Tumor Cell Proliferation Pharmacology chemistry.chemical_classification Chemistry Organic Chemistry Cell Cycle NF-kappa B Prostatic Neoplasms Biological activity Oxides General Medicine Cycloaddition Benzonitrile Colonic Neoplasms Sesquiterpenes Lactone Neoplasm Transplantation |
| Zdroj: | European journal of medicinal chemistry. 46(8) |
| ISSN: | 1768-3254 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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