title: Novel triazole hybrids of myrrhanone C, a natural polypodane triterpene: Synthesis, cytotoxic activity and cell based studies.
abstract: The 3-keto functionality in ring A of myrrhanone C, a natural bicyclic triterpene has been chemically modified and synthesized 27 novel triazole hybrids belonging to two different series in very good to excellent yields (66-83%). The synthesized compounds were thoroughly characterized by their spectroscopic data (IR, (1)H&(13)C NMR, HRMS). All the synthesized compounds were evaluated for their cytotoxic potential against a panel of five human cancer cell lines by employing MTT assay using doxorubicin as the standard. In general the synthesized compounds showed anticancer activity against almost all the cell lines screened. Interestingly, the oxime based triazoles (4a-4n) showed higher activity than the benzylidene triazoles (6a-6m). Most significantly compound 4a showed potent activity against all the tested cell lines, especially against lung cancer (A-549) with an IC 50 of 6.16 μm. In view of their significant activity against lung cancer cell lines, compounds 4a and 4l were subjected to detailed biological studies, which revealed that they arrested cell cycle in G2/M phase and induced cell death by apoptosis that was further confirmed by Hoechst staining, measurement of mitochondrial membrane potential (ΔΨm) and Annexin V-FITC assay. These compounds will serve as lead molecules in the development of potent anticancer drug candidates especially for lung cancer.
authors.affiliation: Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, 500007, India.
authors.forename: Madasu
authors.initials: M
authors.lastname: Chandrashekhar
authors.affiliation: Department of Medicinal Chemistry & Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India.
authors.forename: Vadithe Lakshma
authors.initials: VL
authors.lastname: Nayak
authors.affiliation: Department of Medicinal Chemistry & Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India.
authors.forename: Sistla
authors.initials: S
authors.lastname: Ramakrishna
authors.affiliation: Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, 500007, India. Electronic address: uvmavadani@yahoo.com.
authors.forename: Uppuluri Venkata
authors.initials: UV
authors.lastname: Mallavadhani
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001688:Biological Products; D014230:Triazoles; D014315:Triterpenes; C000613141:myrrhanone C
keywords: Anticancer activity; Hybrids; Myrrhanone C; Triazoles; Triterpene