Abstract
A new series of sixteen N4-aryl substituted 5-chloroisatin-3-thiosemicarbazones 2a-2p has been synthesized, characterized and tested for selected biological activities i.e. cytotoxicity, phytotoxicity and urease inhibition. In the brine shrimp bioassay, all the synthesized compounds gave LD50 values >2.30 X 10-4 M - 2.79 X 10-4 M and were, therefore, found to be almost inactive, whereas in phytotoxicity assay, regardless of the nature of aryl substituents, they displayed weak to moderate (5-40%) phytotoxic activity at the highest tested concentrations (500 or 1000 μg/mL). In urease inhibition bioassay, compounds 2a, 2c, 2e, 2f, 2k and 2m exhibited relatively a higher degree of urease inhibition with IC50 values ranging from 38.91 μM to 76.65 μM and thus proved to be potent inhibitors of the enzyme. Of these, 2f and 2m displayed pronounced inhibition with IC50 values 38.91 μM and 39.50 μM, respectively, and may act as lead compounds for further studies. Structure-activity relationship (SAR) studies revealed that electronic effects of the substituents about the phenyl ring at N4 of the thiosemicarbazone moiety played an important role in enhancing the urease inhibitory potential of some of the synthesized compounds.
Keywords: 5-Chloroisatin, 5-Chloroisatin-3-thiosemicarbazones, Thiosemicarbazones, Cytotoxicity, Phytotoxicity, Soil Ureases Inhibitors, Urease Inhibition, Urease Inhibitors, nickel-dependent, metallo-enzyme
Medicinal Chemistry
Title:Synthesis and Biological Evaluation of Some New N4-Aryl Substituted 5-Chloroisatin-3-thiosemicarbazones
Volume: 8 Issue: 3
Author(s): Humayun Pervez, Muhammad Ramzan, Muhammad Yaqub, Faiz-ul-Hassan Nasim and Khalid Mohammed Khan
Affiliation:
Keywords: 5-Chloroisatin, 5-Chloroisatin-3-thiosemicarbazones, Thiosemicarbazones, Cytotoxicity, Phytotoxicity, Soil Ureases Inhibitors, Urease Inhibition, Urease Inhibitors, nickel-dependent, metallo-enzyme
Abstract: A new series of sixteen N4-aryl substituted 5-chloroisatin-3-thiosemicarbazones 2a-2p has been synthesized, characterized and tested for selected biological activities i.e. cytotoxicity, phytotoxicity and urease inhibition. In the brine shrimp bioassay, all the synthesized compounds gave LD50 values >2.30 X 10-4 M - 2.79 X 10-4 M and were, therefore, found to be almost inactive, whereas in phytotoxicity assay, regardless of the nature of aryl substituents, they displayed weak to moderate (5-40%) phytotoxic activity at the highest tested concentrations (500 or 1000 μg/mL). In urease inhibition bioassay, compounds 2a, 2c, 2e, 2f, 2k and 2m exhibited relatively a higher degree of urease inhibition with IC50 values ranging from 38.91 μM to 76.65 μM and thus proved to be potent inhibitors of the enzyme. Of these, 2f and 2m displayed pronounced inhibition with IC50 values 38.91 μM and 39.50 μM, respectively, and may act as lead compounds for further studies. Structure-activity relationship (SAR) studies revealed that electronic effects of the substituents about the phenyl ring at N4 of the thiosemicarbazone moiety played an important role in enhancing the urease inhibitory potential of some of the synthesized compounds.
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Pervez Humayun, Ramzan Muhammad, Yaqub Muhammad, Nasim Faiz-ul-Hassan and Mohammed Khan Khalid, Synthesis and Biological Evaluation of Some New N4-Aryl Substituted 5-Chloroisatin-3-thiosemicarbazones, Medicinal Chemistry 2012; 8 (3) . https://dx.doi.org/10.2174/1573406411208030505
DOI https://dx.doi.org/10.2174/1573406411208030505 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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