title: Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies.
abstract: The synthesis of novel indolopyrazoline derivatives (P1-P4 and Q1-Q4) has been characterized and evaluated as potential anti-Alzheimer agents through in vitro Acetylcholinesterase (AChE) inhibition and radical scavenging activity (antioxidant) studies. Specifically, Q3 shows AChE inhibition (IC50: 0.68±0.13μM) with strong DPPH and ABTS radical scavenging activity (IC50: 13.77±0.25μM and IC50: 12.59±0.21μM), respectively. While P3 exhibited as the second most potent compound with AChE inhibition (IC50: 0.74±0.09μM) and with DPPH and ABTS radical scavenging activity (IC50: 13.52±0.62μM and IC50: 13.13±0.85μM), respectively. Finally, molecular docking studies provided prospective evidence to identify key interactions between the active inhibitors and the AChE that furthermore led us to the identification of plausible binding mode of novel indolopyrazoline derivatives. Additionally, in-silico ADME prediction using QikProp shows that these derivatives fulfilled all the properties of CNS acting drugs. This study confirms the first time reporting of indolopyrazoline derivatives as potential anti-Alzheimer agents.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Kedah, Malaysia. Electronic address: sridevi.phd@gmail.com.
authors.forename: Sridevi
authors.initials: S
authors.lastname: Chigurupati
authors.affiliation: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia; Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia. Electronic address: manifans@gmail.com.
authors.forename: Manikandan
authors.initials: M
authors.lastname: Selvaraj
authors.affiliation: Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia; Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah 51452, Saudi Arabia.
authors.forename: Vasudevan
authors.initials: V
authors.lastname: Mani
authors.affiliation: Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.
authors.forename: Kesavanarayanan Krishnan
authors.initials: KK
authors.lastname: Selvarajan
authors.affiliation: Department of Pharmacology, Faculty of Medicine, AIMST University, Semeling, 08100 Bedong, Kedah, Malaysia.
authors.forename: Jahidul Islam
authors.initials: JI
authors.lastname: Mohammad
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Kedah, Malaysia.
authors.forename: Balaji
authors.initials: B
authors.lastname: Kaveti
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Kedah, Malaysia.
authors.forename: Hriday
authors.initials: H
authors.lastname: Bera
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Kedah, Malaysia.
authors.forename: Vasanth Raj
authors.initials: VR
authors.lastname: Palanimuthu
authors.affiliation: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia; Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.
authors.forename: Lay Kek
authors.initials: LK
authors.lastname: Teh
authors.affiliation: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia; Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.
authors.forename: Mohd Zaki
authors.initials: MZ
authors.lastname: Salleh
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D007211:Indoles; D011720:Pyrazoles; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase; Antioxidant; Indole; Molecular docking; Pyrazoline