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Unsymmetrical 1,3-disubstituted urea derivatives as α-chymotrypsin inhibitors

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Abstract

The objective of this study was to synthesize potent and/or novel inhibitors for α-chymotrypsin activity. Eighteen derivatives of N-methylphenyl-N′-(alkyl/aryl) urea (118) were synthesized, and their inhibitory effects on α-chymotrypsin enzyme were evaluated. Two compounds exhibited potent inhibitory activities. The most potent, N-(2-methylphenyl)-2-oxo-1-pyrrolidinecarboxamide (15) having a methyl group at ortho position was the most active inhibitor with an IC50 value of 8.10 ± 0.14 μM, which was comparable to standard chymostatin (IC50 = 8.24 ± 0.11 μM). A slightly less potent, N-(2-acetylphenyl)-N′-(3-methylphenyl) urea (10), exhibited an IC50 of 13.6 ± 0.23 μM. Compounds 3, 4, 7, 11, and 13 exhibited moderate activities. The results demonstrated that α-chymotrypsin inhibition is related to the position of the methyl group and the presence of substituent at the nitrogen of the urea bridge. The inhibitory trend suggests that α-chymotrypsin inhibitory activity declines with ortho > meta > para substitution order. In conclusion, our data suggest that the compound 15 may serve as a lead compound for further designing of other potent or novel α-chymotrypsin inhibitors.

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Acknowledgments

The authors gratefully acknowledge the Higher Education Commission (HEC) for granting fellowship to Ph. D. student Ms. Sana Mustafa. Authors are also grateful to Dr. Rafat Ali Siddiqui, Cellular Biochemistry Laboratory, Methodist Research Institute, Room E504, Indianapolis, IN 46202, USA for his kind guidance in the preparation of the manuscript.

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Correspondence to Shahnaz Perveen.

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Perveen, S., Mustafa, S., Latif, M. et al. Unsymmetrical 1,3-disubstituted urea derivatives as α-chymotrypsin inhibitors. Med Chem Res 23, 3585–3592 (2014). https://doi.org/10.1007/s00044-014-0930-3

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  • DOI: https://doi.org/10.1007/s00044-014-0930-3

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