In this thesis, 31 chalcone derivatives (1a-1ae) containing indole and benzothiophene rings were designed and synthesized. Their biological activities in inhibiting cholinesterase (ChE) and monoamine oxidase (MAO) were subsequently investigated. The cholinesterase test results indicated that all compounds exhibited minimal inhibitory effects on acetylcholinesterase (AChE). However, certain compounds demonstrated notable inhibitory effects on butyrylcholinesterase (BuChE), with compounds 1a and 1h showing the strongest inhibition rates of 85.55% and 76.43%, respectively.The findings from the monoamine oxidase experiments indicated that some of the compounds exhibited specific inhibitory effects on monoamine oxidase. Compounds exhibiting inhibitory activity exceeding 50%—specifically, 1c, 1f, 1g, 1v, and 1aa—were further evaluated for their effects on MAO-A and MAO-B enzymatic activities. It was observed that compounds 1c, 1f, and 1aa displayed comparatively superior inhibitory activity against both MAO-A and MAO-B.Results from cytotoxicity assays indicated that the compounds demonstrating enhanced inhibitory activity did not exhibit cytotoxic effects on L929 cells. Additionally, the results of molecular docking of compounds 1a, 1c and 1f showed significant interaction between compounds 1a and 1f with BuChE and between compounds 1c and 1f with MAO-A and MAO-B.
Tang Min
,
Zhang Bin
,
Wang Qiu-shi
,
Fang Chao-hua
,
Hu Li-wei
,
Guan Li-ping
. Design, Synthesis, and Evaluation of Bioactivities of Chalcone Derivatives Containing Indole and Benzothiophene Moieties for Monoamine Oxidase and Cholinesterase Inhibition[J]. Chinese Journal of Organic Chemistry, 0
: 202412042
-202412024
.
DOI: 10.6023/cjoc202412042
[1] Ramirez S.; Koerich S.; Astudillo N.; Gregorio N. D.; Lahham R.A.; Allison T.; Rocha N.P.; Wang F.; Soto C. Int. J. Mol. Sci. 2023, 24, 17087.
[2] Hua K.Y.; Zhao W.J.Folia Neuropathol. 2023, 61, 15-18.
[3] Saleem L.; Zubbair M.M.; Debnath P. Heliyon. 2021, 7, e08502.
[4] Li X.T.Metab Brain Dis. 2022, 37, 581-587.
[5] Arianna P.; Manuela G.; Pierpaolo S.; Francesca J.; Maria D.A.; Giuseppe S. Cell. Mol. Neurobiol. 2018, 38, 817-826.
[6] Tabet N.Age Agein. 2006, 35, 336-338.
[7] Lina H.; Grant S.; Katrin B.; Sonja M.; Simon Y.; Klaus H.; Jürgen E.; Gerald M. Pharmacol.Ther. 2007, 113, 154-164.
[8] Saleh L.Y.; Özdemir S.; Sağlık B.N.; Döndaş H.A.; Altug C. J. Mol. Struct. 2024, 1313, 138667.
[9] Annette M.; Klaus H.; Marlene K.; Matt S.; Ralph M.; Jürgen E.; David C.; Gerald M. Adv.Drug Deliv. 2008, 60, 1463-1470.
[10] Kim C.R.; Choi S.J.; Kwon Y.K.; Kim J.K.; Kim Y.J.; Park, G.G. Biol. Pharm. Bull. 2016, 39, 1130-1136.
[11] Mirjana B.L.; ŠGoran H.P.R. Prog Brain Res. 2021, 261, 379-421.
[12] Wang Q.J.; Ren H.H.; Liu T.Q.; Zhang X.Y. J. Affect. 2024, 351, 8-14.
[13] Salwierz P.; Thapa S.; Taghdiri F.; Vasilevskaya A.; Anastassiadis C.; Wai D.F.T.A.; Golas, C.Tartaglia, M.C. GeroSci. 2024, 46, 783-793.
[14] Mayeli M.; Shafie M.; Shiravi M.; Parvar T. A.; Mirsepassi Z.; Rahiminejad F.; Sattarpour R.; Aghamollaii V.Health Rep. 2024, 7, e2106.
[15] Zhao Y.; Qin Y.; Hu X.; Chen X.; Jiang Y.P.; Jin X.J.; Li G.; Li Z.H.; Yang J.H.; Cui S.Y.; Zhang Y. H.Front. Pharmacol. 2024, 15, 1406127.
[16] Mesa R.R.; Barquera J.A.O.S.D.L.D.; Medellin, G.; Garza, L.A.D.L.; Torres, G.S.; Velazquez, J.O.M.; Aviles, F.S.S.; Martinez, J. Am J Geria Psychiat. 2024, 32, S102-S103.
[17] Fakih N.; Fakhoury M. J Psychiatr Pract. 2024, 30, 181-191.
[18] Oliveira V.M.D.; Rocha, M.N.D.; Roberto, C.H.A.; Lucio, F.N.M.; Marinho, M.M.; Marinho, E.S.; Morais, S.M.D. J. Mol. Struct. 2024, 1302, 137453.
[19] Meghan P.; Zhi L.; Bing Q.; Grace T.; Matthew U.; Reed O.; Rebecca D.; Julia V.; Sheyum S.; Nissim I.; María D.L.P.F.; Mimi, S. H.Sci. Rep. 2023, 13, 10411.
[20] Flavia R.; Claudio C.; Andrea S.; Niccolò S.; Alessandro V.; Nicolas Z.; Michele F.; Ken G.; Ignazio C.C.; Vincent V.D.E.; Stephen, S.; Felice, L.; Andrea, D.B. Eur. Neuropsychopharmacol. 2023, 72, 60-78.
[21] Ji Y.; Yang C.Y.; Pang X.R.; Yan Y.B.; Wu Y.; Geng Z.; Hu W.J.; Hu P.P.; Wu X.Q.; Wang K. NRR. 2024, 20, 326-342.
[22] Lana K.;H, Y.M. Cell. 2023, 12, 763.
[23] Min P.S.; Hyun L.S.; Yan Z.H.; Jeongtae K.; Young J.J.; Jin C.Y.; Soyeon J.; Soyeong S.; Kyungsook J.; Hee J.J.Front Neurosci- Switz. 2023, 17, 1108371.
[24] Daniela M.; Sara M.; Benjamin M.; Joseph B.J.; František D. Front.Pharmacol. 2023, 14, 1196413.
[25] Sang Z.P.; Wang K.R.; Wang H.F.; Wang H.J.; Ma Q.W.; Han X.; Ye M.Y.; Yu L.T.; Liu W.M.Bioorganic Med. Chem. Lett. 2017, 27, 5046-5052.
[26] Asif H.; Al B.K.; Jawaid A.M.; Alam K.Shah. J. Mol. Struct. 2021.
[27] Macklin J.L.; Schwans P.J.Bioorganic Med. Chem. Lett. 2020, 30, 127213.
[28] Singh A.; Sharma S.; Arora S.; Attri S.; Kaur P.; Gulati H.K.; Bhagat K.; Kumar Nitish.; Singh H.; Singh J.V.; Bedi P.M.S. Bioorganic Med. Chem. Lett. 2020, 30, 127477.
[29] Rialette H.;P, P.J.; Anél, P. Bioorg Med Chem Lett. 2022, 77, 129038.
[30] Jawed A.M.; Amena A.; Abuzer A.; Arunkumar T.; A, B.M.; Mohammad, Y.; Salahuddin, A. AcsOmega. 2022, 7, 38207-38245.
[31] Munir S.; Shahid A.; Aslam B.; Ashfaq U.A.; Akash M.S.H.; Ali, M.A.; Almatroudi, A.; Allemailem, K.S.; Rajoka, M.S.R.; Khurshid, M.; Baloch, Z. Evid-based Compl Alt. 2020, 2020, 8836983.
[32] Funahashi R.; Matsuura F.; Ninomiya M.; Okabe S.; Takashima S.; Tanaka K.; Nishina A.; Koketsu M.Bioorg.Chem. 2024, 145, 107229.
[33] Liu W. H.; Zhao D. H.; He Z. W.; Hu Y. M.; Zhu Y. X.; Zhang L. J.; Jin L. H.; Guan L. P.; Wang S. H.Molecules. 2022, 27, 9062.
[34] Tan Q. W.; He L. Y.; Zhang S. S.; He Z. W.; Liu W. H.; Zhang L.; Guan L. P.; Wang S.H. Chem. Biodivers. 2022, 19, e202100610.
[35] Guan L. P.; He Z. W.; Jiang K. L.; Sun X. H.; Tang M.; Liu Y.W.; Wu D. Chem.Biodivers. 2023, 20, e202301271.
