Synthesis and anti-OXPHOS,antitumor activities of DLC modified spinosyn derivatives |
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| Affiliation: | 1. School of Pharmaceutical Sciences, Central South University, Changsha 410013, China;2. School of Life Sciences, Central South University, Changsha 410013, China;3. Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China;1. College of Environmental Science and Engineering, Hunan University, Changsha 410082, PR China;2. Key Laboratory of Environmental Biology and Pollution Control, Hunan University, Ministry of Education, Changsha 410082, PR China;1. Oil & Gas Research Institute of the Russian Academy of Sciences, Gubkina 3 St, Moscow 119333, Russia;2. Gubkin Russian State University of Oil and Gas, Moscow 119333, Russia;3. Gazprom VNIIGAZ LLC, Moscow Region, Razvilka 142717, Russia;1. Department of Engineering Mathematics and Physics, Faculty of Engineering, Giza 12211, Egypt;2. Faculty of Physics, Department of Nonlinear Optics, Umultowska 85, 61-614 Poznań, Poland;3. Department of Chemistry, University of Patras, GR-26500 Patras, Greece;1. Department of Chemistry, Kanchi Mamunivar Centre for Post-Graduate Studies, Puducherry 605 008, India;2. Research and Development Centre, Bharathiar University, Coimbatore 641 046, India;3. Department of Chemistry, Rajiv Gandhi College of Engineering and Technology, Puducherry 605 402, India;4. School of Sciences and Humanities, Vel Tech University, Avadi, Chennai 600 032, India |
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| Abstract: | A series of DLC (delocalized lipophilic cation) modified spinosyn derivatives were synthesized and evaluated for antitumor efficacies both in vitro and in vivo. Cancer cell based antiproliferative assays indicated that the more lipophilic derivatives had stronger inhibitory effects on the tested cancer cell lines. Compound 7b and 8b exhibited strong anti-OXPHOS and apoptosis inducing ability. Notable antitumor efficacies of 7b (5 mg/kg) and 8b (2.5 mg/kg) were observed in the in vivo tumor xenograft experiments, however, lethal toxicities were observed on higher dosages. Our findings indicated that DLC modification is a viable strategy to enhance the anti-OXPHOS and antitumor efficacies of spinosyn derivatives. |
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| Keywords: | Spinosyn Antitumor activity Mitochondria OXPHOS Delocalized lipophilic cation |
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