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QSAR studies of indoyl aryl sulfides and sulfones as reverse transcriptase inhibitors

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Abstract

The inhibitory HIV reverse transcriptase activity of 172 non-nucleoside indoyl aryl sulfones and sulfides is studied with a QSAR analysis, in order to identify the molecular characteristics influencing the interaction with the reverse transcriptase enzyme. This work increases the available QSAR studies of indoyl aryl sulfones and sulfides using the reported experimental EC50 values against HIV-1 wild type (IIIB) in human T-lymphocyte (CEM) cells. Different approaches are proposed, involving 0D, 1D and 2D molecular descriptors from PaDEL freeware, and also based on flexible descriptors from CORAL freeware. Three models are finally presented, which correlate the inhibitory HIV reverse transcriptase activity with good accuracy. It is demonstrated that the established models are predictive in the validation process. The novelty of the present work relies on the development of structure-inhibitory HIV activity relationships, through a computational technique that does not require the knowledge of the molecular conformation during the structural representation. The obtained results would contribute to guide the design of more effective compounds for HIV treatment.

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Acknowledgements

PRD acknowledges the financial support from the National Research Council of Argentina (CONICET) PIP11220130100311 project and to Ministerio de Ciencia, Tecnología e Innovación Productiva for the electronic library facilities. The authors are members of the scientific researcher career of the National Research Council of Argentina (CONICET).

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Authors and Affiliations

  1. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), CONICET, UNLP, Diag. 113y 64, Sucursal 4, C.C. 16, 1900, La Plata, Argentina

    Pablo R. Duchowicz

  2. Departamento de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Belgrano, Villanueva 1324, CP 1426, Buenos Aires, Argentina

    Daniel E. Bacelo & Silvina E. Fioressi

  3. Centro de Investigación y Desarrollo en Ciencias Aplicadas “Dr. J.J. Ronco” (CINDECA), Departamento de Química, Facultad de Ciencias Exactas, CONICET, UNLP, Calle 47 No. 257, B1900AJK, La Plata, Argentina

    Valeria Palermo & Gustavo P. Romanelli

  4. Department of Computer Education, University of Nigeria, Nsukka, Nigeria

    Nnenna E. Ibezim

  5. Cátedra de Química Orgánica, Centro de Investigación en Sanidad Vegetal (CISaV), Facultad de Ciencias Agrarias y Forestales, Universidad Nacional de La Plata, Calles 60y 119s/n, B1904AAN, La Plata, Argentina

    Gustavo P. Romanelli

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  1. Pablo R. Duchowicz
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  2. Daniel E. Bacelo
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  3. Silvina E. Fioressi
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  4. Valeria Palermo
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  5. Nnenna E. Ibezim
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  6. Gustavo P. Romanelli
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Correspondence to Pablo R. Duchowicz or Daniel E. Bacelo.

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Duchowicz, P.R., Bacelo, D.E., Fioressi, S.E. et al. QSAR studies of indoyl aryl sulfides and sulfones as reverse transcriptase inhibitors. Med Chem Res 27, 420–428 (2018). https://doi.org/10.1007/s00044-017-2069-5

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