Screening of caspase-3 inhibitors from natural molecule database using e-pharmacophore and docking studies.

Sasidhar Reddy Eda,Jayakumar Singh Bondili,Ganesh Kumar Veeramachaneni,Rajeswari Jinka

doi:10.6026/97320630015240

Abstract

Caspase a protease family member, have a vital role in cell death and inflammation process. Caspase-3, an effector caspase controls the regulation of apoptosis and has an anti apoptotic function. The mechanical significance of restoring apoptosis signaling to selectively target malignant cells is utilized to develop strong therapeutic strategies by the caspase family of mortality - induction molecules. Caspase-3 has currently no clear role in treatment for tumor progression and tumor sensitivity. The present study was aimed to screen caspase for potential inhibitors using computer aided docking methodologies. For this, zinc natural molecule database molecules were screened using e-pharmacophore and ADME protocols along with docking studies. Docking analysis selected two molecules, namely ZINC13341044 and ZINC13507846 with G-scores -5.27 and -6.19 respectively. These two potential hits are predicted as caspase inhibitors based on the results and can be further processed for in vitro validation.

Highlights

The Extracellular matrix (ECM) receptors are imperative controllers of angiogenesis
Unligated α5β1 integrin inhibits survival and proliferation of the tumor cell even when they adhere to the ECM through different integrins assuming a major role in the direction of cell survival [2, 3]
For certain biochemical and morphological changes during apoptosis, Caspase3 is required. It is a frequently activated death protease, which cleaves a range of important cell proteins with numerous death signals. This is important for cell death in a significant manner based on tissue, cell - type or death stimulus, as it is essential for the implementation and completion of apoptosis in certain types of characteristic cell morphology changes and biochemistry events

Summary

Introduction

The Extracellular matrix (ECM) receptors are imperative controllers of angiogenesis. One of these receptors, integrin α5β1, impact tumor-cell survival, multiplication, and metastasis, since the adversaries of this integrin α5β1 strongly restrain angiogenesis and tumor development [1]. For certain biochemical and morphological changes during apoptosis, Caspase is required It is a frequently activated death protease, which cleaves a range of important cell proteins with numerous death signals. In the plasma membrane of the rat fibroblast cells during late stages of anoikis, our previous data reported the direct interaction between α5β1 integrin and caspase 3. These cells avoid cell death through the interaction of caspase 3 and unligated α5β1 integrins during the non - adherence process [2]. In silico methods became prominent in ISSN 0973-2063 (online) 0973-8894 (print)

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