Abstract
A series of 4-oxycoumarin derivatives was synthesized, characterized and evaluated in vitro and in vivo for antifilarial activity against the human lymphatic filarial parasite, Brugia malayi. A majority of the compounds studied showed potent in vitro activity with low IC50 values in the micro molar (μM) range (0.014-1.73 and 0.0056-0.43) against adult worms and microfilariae, respectively. Compounds 8 and 9 were identified to be the most promising antifilarial candidate molecules exhibiting activity in the nanomolar (nM) range. The IC50 values for compound 8 were 14 nM and 5.6 nM while for compound 9 were 94 nM and 13 nM, respectively, for adult worm and microfilaria. These two compounds also displayed promising adulticidal activity (74.9 ± 4.8% and 69.4 ± 2.8%, respectively) in the primary rodent (jird) screen. This study also serves as a starting point for investigating structure-activity relationship with different amino substituents.
References
Jun 1, 1996·General Pharmacology·J R Hoult, M Payá
Jun 27, 2003·Acta Tropica·R P TripathiP K Murthy
Jan 22, 2004·Arzneimittel-Forschung·Diksha KatiyarJitendra Kumar Saxena
Mar 2, 2005·Parasitology Research·Preeti BajpaiShailja Misra-Bhattacharya
Dec 16, 2006·Current Medicinal Chemistry·Rama Pati TripathiJyoti Pandey
Apr 3, 2008·The Journal of Clinical Investigation·Peter J HotezJulie Jacobson
Apr 21, 2009·Acta Tropica·M KalyanasundaramG Prabakaran
Feb 20, 2010·Current Medicinal Chemistry·M E RiveiroC Davio
May 21, 2010·Bioorganic & Medicinal Chemistry Letters·Santosh S ChhajedSachin S Wazalwar
Apr 28, 2011·Current Medicinal Chemistry·D Katiyar, L K Singh
Apr 28, 2011·Parasitology Research·Sweta MisraShailja Misra-Bhattacharya
Jan 17, 2012·PLoS Neglected Tropical Diseases·Solomon NwakaTimothy Geary
Jan 31, 2012·Bioorganic & Medicinal Chemistry Letters·Koneni V SashidharaP K Murthy
Feb 7, 2012·Experimental Parasitology·Jyoti GuptaShailja Misra-Bhattacharya
Feb 22, 2012·European Journal of Medicinal Chemistry·Koneni V SashidharaShailja Misra-Bhattacharya
Feb 27, 2013·Current Pharmaceutical Design·Xin-Mei PengCheng- He Zhou
Apr 2, 2013·Bioorganic & Medicinal Chemistry Letters·Komal KalaniS K Srivastava
May 28, 2014·European Journal of Medicinal Chemistry·Koneni V SashidharaP K Murthy
Citations
May 14, 2016·Chemico-biological Interactions·Luana G de SouzaJose D Figueroa-Villar
Jul 29, 2016·Pathogens and Disease·Sweta MisraShailja Misra-Bhattacharya
Oct 22, 2016·European Journal of Medicinal Chemistry·Xing-Hai LiuWei-Li Peng
Apr 1, 2018·ChemMedChem·Pankaj Kumar Singh, Om Silakari
Dec 5, 2019·Current Drug Targets·Pone Kamdem Boniface, Ferreira Igne Elizabeth
Mar 16, 2018·ACS Medicinal Chemistry Letters·Sreedhar R TummalapalliDavid P Rotella