Synthesis and biological evaluation of calycanthaceous alkaloid analogs |
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| Institution: | 1. School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003, Jiangsu, China;2. Key Laboratory of Protection & Utilization of Biological Resources in Tarim Basin of Xinjiang Production and Construction Corps/College of Life Sciences, Tarim University, Alar 843300, Xinjiang, China;3. Key Laboratory of Botanical Pesticide R & D in Shaanxi Province, Yangling 712100, Shaanxi, China;1. Strategic Information Department, UNAIDS, 20 Avenue Appia, 1211 Geneva 27, Switzerland;2. Harm Reduction International, London, UK;3. International Network of People who Use Drugs, London, UK;4. HIV, Viral Hepatitis and STI Team, WHO, Hanoi, Vietnam;5. Department of Global HIV, Hepatitis, and STI Programmes, WHO, Geneva, Switzerland;1. Intensive Care Department, Vall d’Hebron University Hospital, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain;2. Shock, Organ Dysfunction and Resuscitation Research Group, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron University Hospital, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain;1. Department of Chemistry & Biochemistry and the Center for Nanoscience, University of Missouri St. Louis, St. Louis, MO 63121, United States;2. Department of Chemistry, Lewis and Clark College, Portland, OR 97219, United States |
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| Abstract: | Starting from 9-methyl-1,2,3,4,9,9a-hexahydro-4aH-pyrido2,3-b]indol-4a-ol, or indole-3-acetonitrile, 40 new calycanthaceous alkaloid analogs were synthesized in excellent yields. The prepared compounds were evaluated for biological activity against acetylcholinesterase and a broad range of plant pathogen fungi. The results of bioassays indicated that the majority of tested compounds displayed comparable or better in vitro bioactivity than the positive control. Notably, compounds b8 and b9 showed higher activity against Verticillium dahlia than chlorothalonil, with MIC values of 62.5 and 7.81 µg mL−1, respectively. Compound b3 had a higher activity against Bacillus cereus, with a MIC value of 15.63 µg mL−1. Compounds c2 and c11 revealed potent activity against acetylcholinesterase, with MIC values of 0.01 and 0.1 ng mL−1, respectively. Analysis of the molecular docking modes of c2 and c11 with Torpedo californica acetylcholinesterase indicated a medium strong hydrogen bond interaction between the hydroxyl groups of both the ligands and the phenolic hydroxyl of Try121 at a distance of approximately 2.4 Å. The results obtained in this study will be useful for the further design and structural optimization of calycanthaceous alkaloids as potential agrochemical lead compounds for plant disease control. |
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| Keywords: | Calycanthaceous alkaloids Synthesis Plant pathogen fungi Acetylcholinesterase SAR |
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