Design,synthesis and biological evaluation of a series of pyrano chalcone derivatives containing indole moiety as novel anti-tubulin agents |
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| Affiliation: | 1. State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Gaopeng Street, Chengdu 610041, China;2. College of Chemistry of Sichuan University, Chengdu 610064, Sichuan, China;1. Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, Uttar pradesh 226031, India;2. Biochemistry Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India;1. Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, India;2. Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan;1. Division of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330 Etiler, Ankara, Turkey;2. Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, 06500 Besevler, Ankara, Turkey;3. Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, United States;4. Department of Women’s and Children’s Health, Laboratory of Oncohematology, University of Padova, 35128 Padova, Italy;1. Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470 Eskişehir, Turkey;2. Anadolu University, Faculty of Pharmacy, Department of Biochemistry, 26470 Eskişehir, Turkey;3. Eskisehir Osmangazi University, Faculty of Medicine, Department of Medical Biochemistry, 26480 Eskişehir, Turkey;1. Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India;2. Faculty of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, India;3. Molecular Modeling and Pharmacoinformatics Lab, Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab 143005, India;4. Lloyd Institute of Management and Technology, Greater Noida, UP, India;5. Indian Institute of Integrative Medicine, Jammu, India;1. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China;2. Department of Medicinal Chemistry, Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, Minneapolis 55414, United States |
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| Abstract: | A new series of pyrano chalcone derivatives containing indole moiety (3–42, 49a–49r) were synthesized and evaluated for their antiproliferative activities. Among all the compounds, compound 49b with a propionyloxy group at the 4-position of the left phenyl ring and N-methyl-5-indoly on the right ring displayed the most potent cytotoxic activity against all tested cancer cell lines including multidrug resistant phenotype, which inhibits cancer cell growth with IC50 values ranging from 0.22 to 1.80 μM. Furthermore, 49b significantly induced cell cycle arrest in G2/M phase and inhibited the polymerization of tubulin. Molecular docking analysis demonstrated the interaction of 49b at the colchicine binding site of tubulin. In experiments in vivo, 49b exerted potent anticancer activity in HepG2 human liver carcinoma in BALB/c nude mice. These results indicated these compounds are promising inhibitors of tubulin polymerization for the potential treatment of cancer. |
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| Keywords: | Millepachine Indole Chalcone Tubulin |
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