Interactions of Indomethacin with Functionalized Rhombellanes – a Molecular Docking Study

Raluca Pop,Dušanka Janežič

doi:10.5562/cca3591

Abstract

The specific properties of carbon-based nanomaterials like fullerenes and graphenes have attracted a continuous interest for their possible use as drug carriers. The functionalization of these nanomaterials can lead to the variation or improvement of the required properties, in order to lead to the design of the most suitable compounds within a specific field. In this regard, the possible use of a new class of nanostructures -the rhombellanes- as nanocarriers is investigated. The aim of the paper is to study the interactions of indomethacin and four analogues with anti-inflammatory activity on 13 rhombellanes (three of them with a hyper-adamantane motif, Ada-rbl, three cube-rhombellane homeomorphs, C-rbl, and seven cube-rhombellane-ether/amine structures). Five compounds with anti-inflammatory activity have been docked to the surface of the rhombellanes; comparisons with the results obtained for fullerene C60 have been performed. The best binding affinities for the indomethacin and its derivatives have been obtained for two types of rhombellanes, Ada-rbl and C-rbl. The indomethacin analogue I4 shows an increased binding affinity for C-rbl.420, similar to the value obtained for C60. Best results have been obtained for rhombellane derivatives characterized by smaller HOMO-LUMO gaps.

Highlights

I NFLAMMATION is a defensive response of the body that causes physiological adaptations in order to minimize tissue damage and eliminate pathogenic infections
Five compounds with anti-inflammatory activity have been docked to the surface of the rhombellanes; comparisons with the results obtained for fullerene C60 have been performed
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat minor pain and manage edema and tissue damage that may occur in arthritis

Summary

Introduction

I NFLAMMATION is a defensive response of the body that causes physiological adaptations in order to minimize tissue damage and eliminate pathogenic infections. Chronic inflammation is an important factor contributing to morbidity and mortality, and may lead to diseases such as arthritis, osteoarthritis, retinitis, multiple sclerosis, psoriasis, and atherosclerosis.[1,2,3]. In this regard, some of the most commonly used classes of compounds are non-steroidal anti-inflammatory drugs; an important representative of this class of compounds being the indomethacin. The therapeutic action of these compounds is manifested by the inhibition of prostaglandin biosynthesis.[4,5,6]

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