In vitro leishmanicidal activity of 3-substituted isocoumarins: synthesis and structure activity relationship.
Twenty-five 3-substituted isocoumarins were synthesized using cutting edge microwave-assisted technology in high yields. The syntheses of different isocoumarins were carried out in a single step by the direct condensation of homophthalic acid with aryol and acyl chlorides under the solvent-free conditions without any solid support. The structures of all the synthesized compounds were characterized using different spectroscopic techniques including UV, IR, (1)HNMR and EIMS and purity was confirmed by CHN analysis. All the synthesized compounds were tested for in vitro leishmanicidal activity. Compounds 3a, 3b, 3g, 3l, 3m, 3r, 3t, 3w, 3x, and 3y displayed potential in vitro leishmanicidal activity with IC(50) values in the range of 0.56-84.38 microg/ml, whereas standard inhibitors amphotericine B have IC(50) = 0.24 microg/ml. The compounds 3b, 3g, 3m, 3t, 3w, 3x, and 3y having IC(50) values 27.86, 28.88, 36.49, 34.37, 28.68, 0.89 and 0.56 microg/ml, respectively, were most active among the present series while remaining others were found less active. The compound 3x and 3y can act as potential lead molecules for further development of isocoumarin-based new drugs for the treatment of leishmaniasis.
Khan
Khalid Mohammed
KM
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi-75270, Pakistan. hassaan2@super.net.pk
Ahmed
Sumbul
S
Khan
Zulfiqar Ali
ZA
Zia-Ullah
Rani
Mubeen
M
Choudhary
Muhammad Iqbal
MI
Perveen
Shahnaz
S
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D049934:Isocoumarins / Q000737:chemistry / Q000494:pharmacology*; D007891:Leishmania / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000981:Antiprotozoal Agents; D049934:Isocoumarins