Abstract
A series of 26 new compounds were synthesized and screened for their anti-human immunodeficiency virus-1 and cytotoxicity activity. Of these, 14 were found to be inhibitors of human immunodeficiency virus replications in primary human lymphocytes with 50 % effective concentration values <20 µM. Moreover, most of the compounds were cytotoxic to human lymphocytes, CEM, and Vero cells. Our structure activity relationship study identified different patterns. Compounds 2g–j and 4 (whose structure is closer to the loviride structure) were very potent. Comparing the activity of the compounds containing the 2-aryl substituents, we observed that compounds with benzyloxyphenyl groups were more potent. Compounds in which the 1-aryl moiety contained methyl group in 4- or 3,5-positions also showed high activity. In the series of compounds containing the nitrile, amine, and amide groups, we observed a decrease in activity with CN > NH2 > C(O)NH2. The difference of activity between the 5-membered and 4-membered rings compounds was not significant. This initial information could be used to design improved anti-human immunodeficiency virus compounds in this class.
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Acknowledgments
The authors are grateful to the Civilian Research and Development Foundation (CRDF) (Grant No. ARB2-2701-YE-05). This work was also facilitated in part by the NIH grant P30-AI-050409 (to RFS). This paper is dedicated to our friend and colleague Dr. Ashot H. Martirosyan who died after a long illness on June 25, 2016.
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Martirosyan, A.H., Gasparyan, S.P., Alexanyan, M.V. et al. Anti-human immunodeficiency activity of novel 2-arylpyrrolidine analogs. Med Chem Res 26, 101–108 (2017). https://doi.org/10.1007/s00044-016-1731-7
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DOI: https://doi.org/10.1007/s00044-016-1731-7