Synthesis and cytotoxicity against KB and NCI-H187 cell lines of sporogen AO-1 analogues |
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| Affiliation: | 1. Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand;2. Natural Products Research Center of Excellence and Department of Microbiology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand;3. National Center for Genetic Engineering and Biotechnology (BIOTEC), Thailand Science Park, Klong Luang, Pathumthani 12120, Thailand;1. Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom;2. Novo Nordisk, Måløv, Denmark;1. RIKEN Center for Sustainable Resource Science, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan;2. Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan;1. Key Laboratory of Tropical Medicinal Plant Chemistry of Ministry of Education, Hainan Normal University, Haikou 571158, PR China;2. Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning 530022, PR China;3. College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, PR China;1. College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, PR China;2. State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, PR China;1. National and Local Union Engineering Research Center of Veterinary Herbal Medicine Resources and Initiative, Hunan Agricultural University, Changsha, 410128, China;2. School of pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China;3. Pharmaceutical Analytical & Solid-State Chemistry Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai 201203, China;1. Department of Resources Science of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China;2. Key Laboratory of Modern Traditional Chinese Medicines, China Pharmaceutical University, Nanjing 210009, China |
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| Abstract: | 20 Analogues of sporogen AO-1 were synthesized by chemical modification at α,β-unsaturated carbonyl, 3-hydroxyl and vinylic methyl groups of sporogen AO-1 precursor, and were evaluated for their cytotoxic activities against human oral epidermoid carcinoma (KB) and human small cell lung (NCI-H187) cancer cell lines. Structure-activity relationship study indicated the importance of α,β-unsaturated carbonyl moiety for both cancer cell lines. Vinylic methyl and R-configuration of 3-hydroxyl group were crucial for cytotoxicity toward KB cells. In contrast, conversion of vinylic methyl and 3-hydroxyl groups to ketone moieties afforded triketone 19 which displayed comparable cytotoxicity against NCI-H187 cells lines to sporogen AO-1, and was more potent than ellipticine, a standard drug. Interestingly, compound 19 was weakly cytotoxic toward Vero cells, whereas sporogen AO-1 showed strong cytotoxicity. |
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| Keywords: | Structure modification Cytotoxicity Oral cavity cancer Lung cancer Structure-activity relationships |
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