Design,synthesis, molecular modeling and biological evaluation of novel 1H-pyrazolo[3,4-b]pyridine derivatives as potential anticancer agents |
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| Institution: | 1. Pharmaceutical Chemistry Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt;2. Chemistry Department, Faculty of Science, Ain Shams University, Abbassiya, Cairo 11566, Egypt;1. Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India;2. Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India;1. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt;2. Pharmaceutical Sciences Department, Ibn Sina National College for Medical Studies, Jeddah 21418, Saudi Arabia;3. Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Al Jouf 2014, Saudi Arabia;1. Department of Chemistry, Faculty of Science, Al-Azhar University, 11284 Nasr City, Cairo, Egypt;2. Department of Chemistry, Faculty of Arts and Science, Northern Border University, Rafha, Saudi Arabia;3. Pharmacology Department, National Research Center, El-Bohoth St., Dokki, P.O. 12622, Cairo, Egypt;4. Department of Chemistry, Faculty of Science and Arts, King Khalid University, Mohail Assir, Saudi Arabia;5. Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt;1. Programa de Pós-Graduação em Patologia - Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Niterói, RJ, Brazil;2. Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA;3. Programa de Pós-Graduação em Ciências Aplicadas a Produtos para Saúde (PPG-CAPS) - Faculdade de Farmácia, Universidade Federal Fluminense, Niterói, RJ, Brazil;4. Programa de Pós-Graduação em Ciências e Biotecnologia (PPBI) - Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, Brazil;5. Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF) - Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, RJ, Brazil;6. Laboratório de Química Medicinal (LQMed) - Faculdade de Farmácia, Universidade Federal Fluminense, Niterói, RJ, Brazil;1. Academy of Scientific & Innovative Research, Natural Products and Green Chemistry Division, CSIR–Central Salt & Marine Chemicals Research Institute, G.B. Marg, Bhavnagar, 364 002, Gujarat, India;2. CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India;1. School of Biological Engineering, Tianjin University of Science and Technology, #29, 13th Avenue, TEDA, Tianjin 300457, China;2. Tianjin Binjiang Pharma, Inc., #238 Baidi Road, Nankai District, Tianjin 300192, China;3. Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, #238 Baidi Road, Nankai District, Tianjin 300192, China |
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| Abstract: | In trying to develop new anticancer agents, a series of 1H-pyrazolo3,4-b]pyridine derivatives was designed and synthesized. Fifteen compounds were evaluated in vitro for their anti-proliferative activity against HePG-2, MCF-7, HCT-116, and PC-3 cell lines. Additionally, DNA binding affinity of the synthesized derivatives was investigated as a potential mechanism for the anticancer activity using DNA/methyl green assay and association constants assay. Compounds 19, 20, 21, 24 and 25 exhibited good activity against the four cancer cells comparable to that of doxorubicin. Interestingly, DNA binding assay results were in agreement with that of the cytotoxicity assays where the most potent anticancer compounds showed good DNA binding affinity comparable to that of doxorubicin and daunorubicin. Furthermore, a molecular docking of the tested compounds was carried out to investigate their binding pattern with the prospective target, DNA (PDB-code: 152d). |
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| Keywords: | Anticancer DNA binding Docking |
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