Synthesis and biological evaluation of coumarin-1,3,4-oxadiazole hybrids as selective carbonic anhydrase IX and XII inhibitors |
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| Institution: | 1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad 500037, India;2. Università degli Studi di Firenze, Neurofarba Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;1. Saint Petersburg State University, Saint Petersburg 199034, Russian Federation;2. Department of Organic Chemistry, Faculty of Science, RUDN University, 117198, Russian Federation;3. The Ushinsky Yaroslavl State Pedagogical University, Yaroslavl 150000, Russian Federation;4. Department of Pharmacy, University of Pisa, 56126 Pisa, Italy;5. Neurofarba Department, Universita degli Studi di Firenze, Florence, Italy;1. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia;2. Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;3. Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, AlKharj, Saudi Arabia;4. Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt;5. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt;1. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia;2. Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;3. Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura, Egypt;1. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran;2. Department of Pharmacology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran;3. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;4. Student Researches Committee, Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Iran;5. Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;6. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran;1. Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland;2. Department of Inorganic Chemistry, Gdańsk University of Technology, Narutowicza 11/12, 80-233 Gdańsk, Poland;3. Dipartimento di Chimica, Universita degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy;4. Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche, 50019 Sesto Fiorentino, Florence, Italy;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt;3. Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy;4. Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy;5. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia;6. Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt |
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| Abstract: | With an aim to develop novel heterocyclic hybrids as potent anticancer agents, we synthesized a series of coumarin-1,3,4-oxadiazole hybrids (7a-t) and evaluated for their inhibitory activity against the four physiologically relevant human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms CA I, CA II, CA IX and CA XII. The CA inhibition results clearly indicated that the coumarin-1,3,4-oxadiazole derivatives (7a-t) exhibited selective inhibition of the tumor associated isoforms, CA IX and CA XII over CA I and II isoforms. Among all, compound 7b, exhibited significant inhibition in lower micromolar potency against hCA XII, with a Ki of 0.16 µM and compound 7n, exhibited significant inhibition in lower micromolar potency against hCA IX, with a Ki of 2.34 µM respectively. Therefore, compound 7b and 7n could be the potential leads for development of selective anticancer agents by exhibiting a novel mechanism of action through hCA IX and XII inhibition. |
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| Keywords: | Coumarin-1 3 4-oxadiazole hybrids Cancer Carbonic anhydrase hCAs I II IX and XII |
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