{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:58:29Z","timestamp":1789793909799,"version":"4.0.1"},"reference-count":48,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T00:00:00Z","timestamp":1692576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Indian Council of Social Science Research (ICSSR)","award":["02\/90\/2022-23\/RP\/MN"],"award-info":[{"award-number":["02\/90\/2022-23\/RP\/MN"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Monoamine oxidase (MAO, EC 1.4.3.4) is responsible for the oxidative breakdown of both endogenous and exogenous amines and exists in MAO-A and MAO-B isomers. Eighteen indole-based phenylallylidene derivatives were synthesized via nucleophilic addition reactions comprising three sub-series, IHC, IHMC, and IHNC, and were developed and examined for their ability to inhibit MAO. Among them, compound IHC3 showed a strong MAO-B inhibitory effect with an IC50 (half-maximal inhibitory concentration) value of 1.672 \u03bcM, followed by IHC2 (IC50 = 16.934 \u03bcM). Additionally, IHC3 showed the highest selectivity index (SI) value of &gt;23.92. The effectiveness of IHC3 was lower than the reference pargyline (0.14 \u03bcM); however, the SI value was higher than pargyline (17.16). Structurally, the IHC (-H in the B-ring) sub-series exhibited relatively stronger MAO-B inhibition than the others. In the IHC series, IHC3 (-F in the A-ring) exhibited stronger MAO-B suppression than the other substituted derivatives in the order -F &gt; -Br &gt; -Cl &gt; -OCH3, -CH3, and -H at the 2-position in the A-ring. In the reversibility and enzyme kinetics experiments, IHC3 was a reversible inhibitor with a Ki value of 0.51 \u00b1 0.15 \u03bcM for MAO-B. Further, it was observed that IHC3 greatly decreased the cell death caused by rotenone in SH-SY5Y neuroblastoma cells. A molecular docking study of the lead molecule was also performed to determine hypothetical interactions in the enzyme-binding cavity. These findings suggest that IHC3 is a strong, specific, and reversible MAO-B inhibitor that can be used to treat neurological diseases.<\/jats:p>","DOI":"10.3390\/molecules28166167","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T09:07:16Z","timestamp":1692608836000},"page":"6167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Assembling a Cinnamyl Pharmacophore in the C3-Position of Substituted Isatins via Microwave-Assisted Synthesis: Development of a New Class of Monoamine Oxidase-B Inhibitors for the Treatment of Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"28","author":[{"given":"Amritha","family":"Manoharan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Min","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feba","family":"Benny","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9035-5638","authenticated-orcid":false,"given":"Mohamed A.","family":"Abdelgawad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia"},{"name":"Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9179-4373","authenticated-orcid":false,"given":"Mohammed M.","family":"Ghoneim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Saudi Arabia"},{"name":"Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed E.","family":"Shaker","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia"},{"name":"Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0814-1743","authenticated-orcid":false,"given":"Mohamed","family":"El-Sherbiny","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh 11597, Saudi Arabia"},{"name":"Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailah M.","family":"Almohaimeed","sequence":"additional","affiliation":[{"name":"Department of Basic Science, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2944-7856","authenticated-orcid":false,"given":"Prashant","family":"Gahtori","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Graphic Era Hill University, Dehradun 248002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7203-3712","authenticated-orcid":false,"given":"Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bijo","family":"Mathew","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.56431\/p-8lif75","article-title":"The chemistry and synthesis of 1H-indole-2,3-dione (isatin) and its derivatives","volume":"7","author":"Sonawane","year":"2013","journal-title":"Int. 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