title: Synthesis of novel anticancer agents through opening of spiroacetal ring of diosgenin.
abstract: Diosgenin has been modified to furostane derivatives after opening the F-spiroacetal ring. The aldehyde group at C26 in derivative 8 was unexpectedly transformed to the ketone 9. The structure of ketone 9 was confirmed by spectroscopy and finally by X-ray crystallography. Five of the diosgenin derivatives showed significant anticancer activity against human cancer cell lines. The most potent molecule of this series i.e. compound 7, inhibited cellular growth by arresting the population at G0/G1 phase of cell division cycle. Cells undergo apoptosis after exposure to the derivative 7 which was evident by increase in sub G0 population in cell cycle analysis. Docking experiments showed caspase-3 and caspase-9 as possible molecular targets for these compounds. This was further validated by cleavage of PARP, a caspase target in apoptotic pathway. Compound 7 was found non-toxic up to 1000mg/kg dose in acute oral toxicity in Swiss albino mice.
authors.affiliation: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India; Department of Chemistry, University of Ilorin, Ilorin, Nigeria.
authors.forename: A A
authors.initials: AA
authors.lastname: Hamid
authors.affiliation: CSIR-Central Drug Research Institute (CSIR-CDRI), B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hasanain
authors.affiliation: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India.
authors.forename: Arjun
authors.initials: A
authors.lastname: Singh
authors.affiliation: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India.
authors.forename: Balakishan
authors.initials: B
authors.lastname: Bhukya
authors.affiliation: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India.
authors.lastname: Omprakash
authors.affiliation: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India.
authors.forename: Prema G
authors.initials: PG
authors.lastname: Vasudev
authors.affiliation: CSIR-Central Drug Research Institute (CSIR-CDRI), B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Sarkar
authors.affiliation: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Chanda
authors.affiliation: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India.
authors.forename: Feroz
authors.initials: F
authors.lastname: Khan
authors.affiliation: Organic Chemistry Unit, Department of Chemistry, University of Ibadan, Ibadan, Nigeria.
authors.forename: O O
authors.initials: OO
authors.lastname: Aiyelaagbe
authors.affiliation: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India. Electronic address: arvindcimap@rediffmail.com.
authors.forename: Arvind S
authors.initials: AS
authors.lastname: Negi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D004144:Diosgenin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D013141:Spiro Compounds / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D013141:Spiro Compounds; D004144:Diosgenin
keywords: Acute oral toxicity; Anticancer; Caspase; Cell cycle; Diosgenin; X-ray crystallography