title: Design, synthesis and biological evaluation of small molecules as potent glucosidase inhibitors.
abstract: Herein we have reported design, synthesis and in vitro biological evaluation of a library of bicyclic lactams that led to the discovery of compounds 6 and 7 as a novel class of α-glucosidase inhibitors. They inhibited α-glucosidase (yeast origin) in a mixed type of inhibition with an IC50 of ∼150 nM. Molecular docking studies further substantiated screening results. Interestingly phenotypic screening of this library against the human malaria parasite revealed 7 as a potent antiplasmodial agent.
authors.affiliation: Department of Chemistry, School of Natural Sciences, Shiv Nadar University, UP 201314, India.
authors.forename: Santanu
authors.initials: S
authors.lastname: Hati
authors.affiliation: Department of Chemistry, Mahatma Gandhi University, Ri Bhoi, Meghalaya, India.
authors.forename: Sanjay M
authors.initials: SM
authors.lastname: Madurkar
authors.affiliation: Department of Chemistry, School of Natural Sciences, Shiv Nadar University, UP 201314, India.
authors.forename: Chandramohan
authors.initials: C
authors.lastname: Bathula
authors.affiliation: Institute of Science, Jawaharlal Nehru Technical University, Kukatpally, Hyderabad, Telangana, India.
authors.forename: Chiranjeevi
authors.initials: C
authors.lastname: Thulluri
authors.affiliation: Department of Life Science, School of Natural Sciences, Shiv Nadar University, UO 201314, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors.forename: Faiza Amber
authors.initials: FA
authors.lastname: Siddiqui
authors.affiliation: Department of Life Science, School of Natural Sciences, Shiv Nadar University, UO 201314, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Dangi
authors.affiliation: Institute of Science, Jawaharlal Nehru Technical University, Kukatpally, Hyderabad, Telangana, India.
authors.forename: Uma
authors.initials: U
authors.lastname: Adepally
authors.affiliation: Department of Life Science, School of Natural Sciences, Shiv Nadar University, UO 201314, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Life Science, School of Natural Sciences, Shiv Nadar University, UO 201314, India.
authors.forename: Shailja
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Chemistry, School of Natural Sciences, Shiv Nadar University, UP 201314, India. Electronic address: subhabrata.sen@snu.edu.in.
authors.forename: Subhabrata
authors.initials: S
authors.lastname: Sen
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005959:Glucosidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D008958:Models, Molecular; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D004791:Enzyme Inhibitors; D054852:Small Molecule Libraries; D005959:Glucosidases
keywords: Alpha-glucosidase; Antiplasmodial; Dihydroxylation; Epoxidation; Virtual screening