Bioactivity-guided isolation of cytotoxic constituents from stem–bark of Premna tomentosa

• Published in: Bioorganic & medicinal chemistry letters 2009-10, Vol.19 (19), p.5727-5731
• Main Authors: Hymavathi, A., Suresh Babu, K., Naidu, V.G.M., Rama Krishna, S., Diwan, Prakash V., Madhusudana Rao, J.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - toxicity; Biological and medical sciences; Cell Line, Tumor; Cytotoxic activity; Diterpenes - chemistry; Diterpenes - isolation & purification; Diterpenes - toxicity; Diterpenoids; Drug Screening Assays, Antitumor; General pharmacology; HT29 Cells; Humans; Icetexanes; Medical sciences; Molecular Conformation; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Plant Bark - chemistry; Premna tomentosa; Verbenaceae; Verbenaceae - chemistry
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.08.002

Bioactivity-guided column chromatographic separation of hexane extract led to the isolation of four new cytotoxic icetexane diterpenes ( 1– 4), along with five known compounds ( 5– 9). Compounds 1– 3 were tested against the cancer cell lines for their cytotoxicity. A bioassay-guided fractionation and chemical investigation of the stem bark of Premna tomentosa resulted in the isolation and characterization of four new icetexane diterpenes ( 1– 4), along with the known compounds coniferaldehyde ( 5), syringaldehyde ( 6), lupeol ( 7), betulin ( 8), and 2-(4-methoxyphenyl)-2-butanone ( 9). Their structures were established on the basis of extensive spectroscopic (IR, MS, 2D NMR) data analysis and by comparison with the spectroscopic data reported in the literature. The new compounds exhibited diverse functionalities on a common icetexane diterpene skeleton. In addition, cytotoxic activities of the icetexanes ( 1– 3) were evaluated by determining their inhibitory effects on the human cancer cell lines (MCF-7, HT-29, Hep-G2, A-431, and A-549). Compounds 1 and 3 showed selective inhibitory activity against MCF-7 (15.96 μg/mL and 15.84 μg/mL) and HT-29 cell lines (16.21 μg/mL and 14.57 μg/mL), respectively.