A Quantitative Structure-Activity Relationships (QSAR) Study of Piperine Based Derivatives with Leishmanicidal Activity

Edilson Beserra Alencar Filho, Joseph Wallace Castro Silva

Abstract


Leishmaniasis is a parasitic disease which represents a serious public health problem in developing countries. It is considered a neglected tropical disease, for which there is little initiative in the search for therapeutic alternatives by pharmaceutical industry. Natural products remain a great source of inspiration for obtaining bioactive molecules. In 2010, Singh and co-workers published the synthesis and in vitro biological activity of piperoyl-aminoacid conjugates, as well as of piperine, against cellular cultures of Leishmania donovani. The piperine is an alkaloid isolated from Piper nigrum that has many activities described in the literature. In this work, we present a Quantitative Structure-Activity Study of piperine derivatives tested by Singh and co-workers, aiming to highlight important molecular features for leishmanicidal activity, obtaining a mathematical model to predict the activity of new analogs. Compounds were submitted to a geometry optimization computational procedure at semiempirical level of quantum theory. Molecular descriptors for the set of compounds were calculated by E-Dragon online plataform, followed by a variable selection procedure using Ordered Predictors Selection algorithm. Validation parameters obtained showed that a good QSAR model, based on multiple linear regression, was obtained (R2 = 0.85; Q2 = 0.69), and the following conclusions regarding the structure-activity relationship were elucidated: Compounds with electronegative atoms on different substituent groups of analogs, absence of unsaturation on lateral chain, presence of ester instead of carboxyl, and large volumes (due the presence of additional aromatic rings) trends to increase the activity against promastigote forms of leishmania.

 

DOI: http://dx.doi.org/10.17807/orbital.v9i1.893



Keywords


E-Dragon; leishmanicidal activity; ordered predictors selection; piperine analogs; QSAR study

Full Text: PDF

Refbacks

  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

Orbital: The Electronic Journal of Chemistry (e-ISSN 1984-6428) is a quarterly scientific journal published by the Institute of Chemistry of the Universidade Federal de Mato Grosso do Sul, Brazil. Orbital is a peer-reviewed, open-access journal.