title: Synthesis and in vitro cytotoxicity of novel C-12 substituted-14-deoxy-andrographolide derivatives as potent anti-cancer agents.
abstract: Andrographolide, the major labdane diterpenoid from Andrographis paniculata has been reported to be cytotoxic against various cancer cells in vitro. Our research efforts led to the discovery of novel 12-phenyl thio and 12-aryl amino-14-deoxy-andrographolide derivatives (III q and III r) with potent cytotoxic activity, 12-benzyl amino-14-deoxy-andrographolide analogues showing broad range of cytotoxic activity against most of the cell lines and 12-alkyl amino-14-deoxy-andrographolide derivatives being selective to few cell lines (PC-3 and HOP-92), when the selected analogues were evaluated against 60 human cancer cell line panel at National Cancer Institute (N.C.I.), USA. The SAR (structure activity relationship) studies demonstrated potent activity for the compounds containing the following functionalities at C-12: substituted aryl amino/phenyl thio>benzylamine>alkyl amine. The significant cytotoxic activity observed for compounds III q and III r suggest that these could serve as templates for further optimization.
authors.affiliation: Department of Chemistry, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam Campus, Prasanthi Nilayam 515134, Anantapur District, Andhra Pradesh, India. Electronic address: skandanur@gmail.com.
authors.forename: Sai Giridhar Sarma
authors.initials: SG
authors.lastname: Kandanur
authors.affiliation: Department of Chemistry, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam Campus, Prasanthi Nilayam 515134, Anantapur District, Andhra Pradesh, India. Electronic address: gnageswararao@sssihl.edu.in.
authors.forename: Nageswara Rao
authors.initials: NR
authors.lastname: Golakoti
authors.affiliation: Department of Process Chemistry, National Institute of Pharmaceutical Education and Research, Balanagar, 500037 Hyderabad, Telangana, India. Electronic address: nandurisrini92@gmail.com.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Nanduri
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; C030419:andrographolide
keywords: 12-Amino andrographolide; Alkyl amines; Anti-cancer activity; Benzyl amines; Sulfonamide; Thiophenol