Carbazole-based semicarbazones and hydrazones as multifunctional anti-Alzheimer agents. Issue 20 (29th November 2022)

• Record Type: Journal Article
• Authors: Patel, Kishan B.; Patel, Dushyant V.; Patel, Nirav R.; Kanhed, Ashish M.; Teli, Divya M.; Gandhi, Bhumi; Shah, Bhavik S.; Chaudhary, Bharat N.; Prajapati, Navnit K.; Patel, Kirti V.; Yadav, Mange Ram
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 40:Issue 20(2022)
• Page Start: 10278
• Page End: 10299
• Publication Date: 2022-11-29
• Subjects: Acetylcholinesterase -- butyrylcholinesterase -- metal chelation -- MTDL -- carbazole -- Alzheimer's disease; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2021.1942212
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: With the aim to combat a multi-faceted neurodegenerative Alzheimer's disease (AD), a series of carbazole-based semicarbazide and hydrazide derivatives were designed, synthesized and assessed for their cholinesterase (ChE) inhibitory, antioxidant and biometal chelating activity. Among them, ( E )-2-((9-ethyl-9 H -carbazol-3-yl)methylene)- N -(pyridin-2-yl)hydrazinecarbothioamide (62 ) and ( E )-2-((9-ethyl-9 H -carbazol-3-yl)methylene)- N -(5-chloropyridin-2-yl)hydrazinecarbothioamide (63 ) emerged as the premier candidates with good ChE inhibitory activities (IC50 values of 1.37 µM and 1.18 µM for h AChE, IC50 values of 2.69 µM and 3.31 µM for Eq BuChE, respectively). All the test compounds displayed excellent antioxidant activity (reduction percentage of DPPH values for compounds (62 ) and (63 ) were 85.67% and 84.49%, respectively at 100 µM concentration). Compounds (62 ) and (63 ) conferred specific copper ion chelating property in metal chelation study. Molecular docking studies of compounds (62 ) and (63 ) indicate strong interactions within the active sites of both the ChE enzymes. Besides that, these compounds also exhibited significant in silico drug-like pharmacokinetic properties. Thus, taken together, they can serve as a starting point in the designing of multifunctional ligands in pursuit of potential anti-AD agents that might further prevent the progression of ADs. Communicated by Ramaswamy H. Sarma