title: Designing, synthesis of selective and high-affinity chalcone-benzothiazole hybrids as Brugia malayi thymidylate kinase inhibitors: In vitro validation and docking studies.
abstract: In our continuing search for safe and efficacious antifilarials, a series of novel chalcone-benzothiazole hybrids have been synthesized and evaluated for their Brugia malayi thymidylate kinase (BmTMK) enzyme inhibition activity. Their selectivity towards BmTMK was studied and compared to the human TMK (HsTMK) by an in silico method. Out of seventeen derivatives, compounds 34 and 42 showed higher interactions with the BmTMK active site. MolDock docking model revealed the interactions of these two derivatives and the results corroborated well with their in vitro antifilarial activities. Our studies suggest that these hybrids are selective towards the BmTMK enzyme and may serve as potential therapeutic agents against filariasis.
authors.affiliation: Medicinal and Process Chemistry Division, BS-10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow 226031, India. Electronic address: sashidhar123@gmail.com.
authors.forename: Koneni V
authors.initials: KV
authors.lastname: Sashidhara
authors.affiliation: Medicinal and Process Chemistry Division, BS-10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Srinivasa Rao
authors.initials: SR
authors.lastname: Avula
authors.affiliation: Biochemistry Division, BS-10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Pawan Kumar
authors.initials: PK
authors.lastname: Doharey
authors.affiliation: Medicinal and Process Chemistry Division, BS-10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow 226031, India.
authors.forename: L Ravithej
authors.initials: LR
authors.lastname: Singh
authors.affiliation: Medicinal and Process Chemistry Division, BS-10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Vishal M
authors.initials: VM
authors.lastname: Balaramnavar
authors.affiliation: Parasitology Divion, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Gupta
authors.affiliation: Parasitology Divion, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Shailja
authors.initials: S
authors.lastname: Misra-Bhattacharya
authors.affiliation: Department of Biochemistry, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Sushma
authors.initials: S
authors.lastname: Rathaur
authors.affiliation: Medicinal and Process Chemistry Division, BS-10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Saxena
authors.affiliation: Biochemistry Division, BS-10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Jitendra Kumar
authors.initials: JK
authors.lastname: Saxena
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017178:Brugia malayi / Q000187:drug effects / Q000201:enzymology*; D002599:Chalcone / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005368:Filariasis / Q000188:drug therapy / Q000469:parasitology; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009703:Nucleoside-Phosphate Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D021261:Parasitic Sensitivity Tests; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship
chemical_list: D052160:Benzothiazoles; D047428:Protein Kinase Inhibitors; D002599:Chalcone; D009703:Nucleoside-Phosphate Kinase; C020093:dTMP kinase
keywords: Antifilarial activity; Benzothiazole; Brugia malayi; Chalcone; Docking studies; Thymidylate kinase