Elucidation of molecular targets of bioactive principles of black cumin relevant to its anti-tumour functionality - An Insilico target fishing approach

TL;DR

This study employs in silico reverse screening and molecular docking to identify potential molecular targets of black cumin's bioactive compounds, elucidating their anti-tumour mechanisms and demonstrating the effectiveness of computational approaches in target identification.

Contribution

It introduces a novel in silico reverse screening approach to identify molecular targets of black cumin's bioactive compounds related to anti-tumour activity, validated by molecular docking.

Findings

Identified putative targets of black cumin compounds relevant to anti-tumour effects.

Validated molecular interactions between thymoquinone and VEGF2.

Demonstrated the effectiveness of in silico methods in target fishing.

Abstract

Black cumin (Nigella sativa) is a spice having medicinal properties with pungent and bitter odour. It is used since thousands of years to treat various ailments, including cancer mainly in South Asia and Middle Eastern regions. Substantial evidence in multiple research studies emphasizes about the therapeutic importance of bioactive principles of N. sativa in cancer bioassays; however, the exact mechanism of their anti-tumour action is still to be fully comprehended. The current study makes an attempt in this direction by exploiting the advancements in the Insilico reverse screening technology. In this study, three different Insilico Reverse Screening approaches have been employed for identifying the putative molecular targets of the bioactive principles in Black cumin (thymoquinone, alpha-hederin, dithymoquinone and thymohydroquinone) relevant to its anti-tumour functionality. The identified set of putative targets is further compared with the existing set of experimentally validated targets, so as to estimate the performance of insilico platforms. Subsequently, molecular docking simulations studies were performed to elucidate the molecular interactions between the bioactive compounds & their respective identified targets. The molecular interactions of one such target identified i.e. VEGF2 along with thymoquinone depicted one H-bond formed at the catalytic site. The molecular targets identified in this study need further confirmatory tests on cancer bioassays, in order to justify the research findings from Insilico platforms. This study has brought to light the effectiveness of usage of Insilico Reverse Screening protocols to characterise the un-identified target-ome of poly pharmacological bioactive agents in spices.