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Discovery of Aporphine Analogues as Potential Antiplatelet and Antioxidant Agents: Design, Synthesis, Structure–Activity Relationships, Biological Evaluations, and in silico Molecular Docking Studies
Author(s) -
Sharma Vashundhra,
Jaiswal Pradeep K.,
Kumar Surendra,
Mathur Manas,
Swami Ajit K.,
Yadav Dharmendra K.,
Chaudhary Sandeep
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800318
Subject(s) - chemistry , stereochemistry , quinoline , dpph , aporphine , ascorbic acid , antioxidant , organic chemistry , alkaloid , food science
To explore the potential of aporphine alkaloids, a novel series of functionalized aporphine analogues with alkoxy (OCH 3 , OC 2 H 5 , OC 3 H 7 ) functional groups at C1/C2 of ring A and an acyl (COCH 3 and COPh) or phenylsulfonyl (SO 2 Ph and SO 2 C 6 H 4 ‐3‐CH 3 ) functionality at the N6 position of ring B of the aporphine scaffold were synthesized and evaluated for their arachidonic acid (AA)‐induced antiplatelet aggregation inhibitory activity and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) free‐radical‐scavenging antioxidant activity, with acetylsalicylic acid and ascorbic acid as standard references, respectively. The preliminary structure–activity relationship related to AA‐induced platelet aggregation inhibitory activity results showed that the aporphine analogues 1‐[1,2,9,10‐tetramethoxy‐6 a ,7‐dihydro‐4 H ‐dibenzo[ de , g ]quinolin‐6(5 H )‐yl]ethanone and 1‐[2‐(benzyloxy)‐1,9,10‐trimethoxy‐6 a ,7‐dihydro‐4 H ‐dibenzo[ de , g ]quinolin‐6(5 H )‐yl]ethanone to be the best compounds of the series. Moreover, the DPPH free‐radical‐scavenging antioxidant activity results demonstrated that the aporphine analogues 1,2,9,10‐tetramethoxy‐6‐(methylsulfonyl)‐5,6,6 a ,7‐tetrahydro‐4 H ‐dibenzo[ de , g ]quinoline, 2‐ethoxy‐1,9,10‐trimethoxy‐6‐(methylsulfonyl)‐5,6,6 a ,7‐tetrahydro‐4 H ‐dibenzo[ de , g ]quinoline, 1‐ethoxy‐2,9,10‐trimethoxy‐6‐(methylsulfonyl)‐5,6,6 a ,7‐tetrahydro‐4 H ‐dibenzo[ de , g ]quinoline, 2,9,10‐trimethoxy‐6‐(methylsulfonyl)‐1‐propoxy‐5,6,6 a ,7‐tetrahydro‐4 H ‐dibenzo[ de , g ]quinoline, and 1‐(benzyloxy)‐2,9,10‐trimethoxy‐6‐(methylsulfonyl)‐5,6,6 a ,7‐tetrahydro‐4 H ‐dibenzo[ de , g ]quinoline were the best compounds of the series. Moreover, in silico molecular docking simulation studies of the active analogues were also performed.