Design,synthesis and biological evaluation of novel hybrids of N-aryl pyrrothine-base α-pyrone as bacterial RNA polymerase inhibitors |
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| Institution: | 1. College of Pharmacy, Guilin Medical University, Guilin 541004, China;2. Department of Pharmacy, Liuzhou People’s Hospital, Liuzhou 545006, China;3. Zhejiang Hisun Pharmaceutical Co., Ltd, Taizhou 318000, China;4. School of Life Sciences, Guangzhou University, Guangzhou 510006, China;1. Laboratory of Advanced Materials Chemistry, Advanced Institute of Materials Science, Ton Duc Thang University, Ho Chi Minh City, Viet Nam;2. Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Viet Nam;3. College of Pharmacy, Yeungnam University, Gyeongbuk 38541, Republic of Korea;4. Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea;5. Laboratories of Marine New Drugs, REDONE Seoul, Seoul 08594, Republic of Korea;6. Department of Convergence Study on the Ocean Science and Technology, Korea Maritime and Ocean University, Busan 49112, Republic of Korea;1. Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland;2. Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm?tna Street, 30-343 Kraków, Poland;1. Department of Chemistry, Duke University, Durham, NC 27708-0354 USA;2. Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710 USA;3. Duke Cancer Institute Center of Prostate and Urologic Cancers, Duke University, Durham, NC 27710 USA;1. Shanghai Key Lab of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, 1239 Siping Road, 200092 Shanghai, China;2. State Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan University, 2005 Songhu Road, 200438 Shanghai, China;3. School of Pharmacy, Nantong University, 19 Qixiu Road, 226001 Nantong, China |
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| Abstract: | Antibiotic resistance in bacteria has been an emerging public health problem, thus discovery of novel and effective antibiotics is urgent. A series of novel hybrids of N-aryl pyrrothine-base α-pyrone hybrids was designed, synthesized and evaluated as bacterial RNA polymerase (RNAP) inhibitors. Among them, compound 13c exhibited potent antibacterial activity against antibiotic-resistant S. aureus with the minimum inhibitory concentration (MIC) in the range of 1–4 μg/mL. Moreover, compound 13c exhibited strong inhibitory activity against E.coli RNAP with IC50 value of 16.06 μM, and cytotoxicity in HepG2 cells with IC50 value of 7.04 μM. The molecular docking study further suggested that compound 13c binds to the switch region of bacterial RNAP. In summary, compound 13c is a novel bacterial RNAP inhibitor, and a promising lead compound for further optimization. |
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| Keywords: | Bacterial RNA polymerase Switch region Hybrid |
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