Anti-tubercular activity of novel 4-anilinoquinolines and 4-anilinoquinazolines |
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| Affiliation: | 1. Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;2. Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;3. Seattle Children’s Research Institute, Seattle, WA 98109, USA;4. Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;5. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;6. Department of Global Health, University of Washington, Seattle, WA 98195, USA;1. Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, Punjab, India;2. Institut de Recherche en Infectiologie (IRIM) de Montpellier, CNRS, UMR 9004 Université de Montpellier, France;3. INSERM, IRIM, 34293 Montpellier, France;4. School of Chemistry and Physics, University of KwaZulu-Natal, P/Bag X54001, Westville, Durban, South Africa;1. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo 11566, Egypt;2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo 11566, Egypt;3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt;4. Pharmacognosy Department, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo 11566, Egypt;5. Center for Drug Discovery and Development Research, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo 11566, Egypt;1. NorthShore University HealthSystem, Dept. of Radiation Medicine, Evanston, IL, USA;2. Oakton Community College, Des Plaines, IL, USA;3. Swiss Tropical and Public Health Institute, Parasite Chemotherapy, Basel, Switzerland;4. University of Basel, Basel, Switzerland;1. Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India;2. Division of Microbiology, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow 226031, India;1. Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai 400019, India;2. Radiation Medicine Centre, Tata Memorial Hospital, Parel, Mumbai 400012, India |
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| Abstract: | We screened a series of 4-anilinoquinolines and 4-anilinoquinazolines and identified novel inhibitors of Mycobacterium tuberculosis (Mtb). The focused 4-anilinoquinoline/quinazoline scaffold arrays yielded compounds with high potency and the identification of 6,7-dimethoxy-N-(4-((4-methylbenzyl)oxy)phenyl)quinolin-4-amine (34) with an MIC90 value of 0.63–1.25 µM. We also defined a series of key structural features, including the benzyloxy aniline and the 6,7-dimethoxy quinoline ring, that are important for Mtb inhibition. Importantly the compounds showed very limited toxicity and scope for further improvement by iterative medicinal chemistry. |
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| Keywords: | Anti-tubercular 4-Anilinoquinoline 4-Anilinoquinazoline |
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