Designing, synthesis of selective and high-affinity chalcone-benzothiazole hybrids as Brugia malayi thymidylate kinase inhibitors: In vitro validation and docking studies

作者：Sashidhara Koneni V^*; Avula Srinivasa Rao; Doharey Pawan Kumar; Singh L Ravithej; Balaramnavar Vishal M; Gupta Jyoti; Misra Bhattacharya Shailja; Rathaur Sushma; Saxena Anil K; Saxena Jitendra Kumar

来源：European Journal of Medicinal Chemistry, 2015, 103: 418-428.

DOI：10.1016/j.ejmech.2015.09.004

• Chalcone
• Benzothiazole
• Thymidylate kinase
• Antifilarial activity
• Brugia malayi
• Docking studies

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.

• 出版日期2015-10-20