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Synthesis and effect of substituent position on anti-inflammatory activity of 3-(halobenzyl)isocarbostyrils

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Abstract

A series of new natural product skeleton based 3-(halobenzyl)isocarbostyrils (2a–2i), were designed and synthesized to examine the effect of position of different halide substituents on anti-inflammatory activity. The structure–activity relationship shows a significant influence of position of halide substituents on in vitro anti-inflammatory activity. 3-(o-halobenzyl)isocarbostyrils (2a, 2d, and 2g) showed the lowest activity most probably due to the closure of pharmacophore site by intramolecular hydrogen bond between halides and N–H of amide. In contrast, 3-(p-halobenzyl)isocarbostyrils 2c, 2f, and 2i exhibited moderate to very good inflammatory activity. Compound 2c (IC50 = 251.002 ± 2.910) was found to have comparable activity with the standard drug (Indomethacin, IC50 = 271.210 ± 2.127). To further understand the effect of position of halide substituents on 3-(halobenzyl)isocarbostyrils, computational POM was carried out. The study with constructive propositions may be helpful for the design of more potent analogs.

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Acknowledgments

The authors are grateful to the Higher Education Commission (HEC) of Pakistan for financial support.

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Authors and Affiliations

  1. Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan

    Tariq Mahmood Babar, Muhammad Moazzam Naseer, Farukh Iftakhar Ali & Nasim Hasan Rama

  2. Laboratoire de Chimie des Matériaux (LCM), Faculté des Sciences d’Oujda (FSO), Université Mohammed 1Er, 60000, Oujda, Morocco

    Taibi Ben Hadda

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  1. Tariq Mahmood Babar
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  2. Muhammad Moazzam Naseer
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Correspondence to Muhammad Moazzam Naseer.

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Babar, T.M., Naseer, M.M., Ali, F.I. et al. Synthesis and effect of substituent position on anti-inflammatory activity of 3-(halobenzyl)isocarbostyrils. Med Chem Res 23, 4607–4618 (2014). https://doi.org/10.1007/s00044-014-1027-8

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  • DOI: https://doi.org/10.1007/s00044-014-1027-8

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