title: In Silico Exploration for New Antimalarials: Arylsulfonyloxy Acetimidamides as Prospective Agents.
abstract: A strategy is described to identify new antimalarial agents to overcome the drug resistance and/or failure issues through in silico screening of multiple biological targets. As a part of this, three enzymes namely CTPS, CK, and GST were selected, from among 56 drug targets of P. falciparum, and used them in virtual screening of ZINC database entries which led to the design and synthesis of arylsulfonyloxy acetimidamides as their consensus inhibitors. From these, two compounds showed good activity against sensitive (3D7; IC50, 1.10 and 1.45 μM) and resistant (K1; IC50, 2.10 and 2.13 μM) strains of the parasite, and they were further investigated through docking and molecular dynamics simulations. The findings of this study collectively paved the way for arylsulfonyloxy acetimidamides as a new class of antimalarial agents.
authors.affiliation: Medicinal and Process Chemistry Division, ‡Parasitology Division, CSIR-Central Drug Research Institute , Jankipuram Extension, Lucknow-226 031, India.
authors.forename: Saroj
authors.initials: S
authors.lastname: Verma
authors.affiliation: Medicinal and Process Chemistry Division, ‡Parasitology Division, CSIR-Central Drug Research Institute , Jankipuram Extension, Lucknow-226 031, India.
authors.forename: Utsab
authors.initials: U
authors.lastname: Debnath
authors.affiliation: Medicinal and Process Chemistry Division, ‡Parasitology Division, CSIR-Central Drug Research Institute , Jankipuram Extension, Lucknow-226 031, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Agarwal
authors.affiliation: Medicinal and Process Chemistry Division, ‡Parasitology Division, CSIR-Central Drug Research Institute , Jankipuram Extension, Lucknow-226 031, India.
authors.forename: Kumkum
authors.initials: K
authors.lastname: Srivastava
authors.affiliation: Medicinal and Process Chemistry Division, ‡Parasitology Division, CSIR-Central Drug Research Institute , Jankipuram Extension, Lucknow-226 031, India.
authors.forename: Yenamandra S
authors.initials: YS
authors.lastname: Prabhakar
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000494:pharmacology*; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D019731:Carbon-Nitrogen Ligases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D002797:Choline Kinase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D062313:Databases, Pharmaceutical; D055808:Drug Discovery; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology*; D013457:Sulfur Compounds / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000577:Amides; D000962:Antimalarials; D004791:Enzyme Inhibitors; D013457:Sulfur Compounds; D005982:Glutathione Transferase; D002797:Choline Kinase; D019731:Carbon-Nitrogen Ligases; C019951:CTP synthetase