Analysis of Weak Interactions in Crystals of Fenamic Acids–Ethacridine Complexes

Marta S Krawczyk,Irena Majerz

doi:10.1021/acs.cgd.1c00768

Abstract

While searching for new drugs based on combinations of fenamic acid and its derivatives with other pharmaceutically active substances, the syntheses of complexes of fenamic, flufenamic, mefenamic, and tolfenamic acids with ethacridine lactate were performed, and obtained complexes were characterized by X-ray diffraction. The inter- and intramolecular interactions were determined. An analysis of hydrogen bonds and other weak interactions was performed using Quantum Theory of Atoms in Molecules and noncovalent interaction approaches. The main force building the hydrogen-bond system are proton-accepting properties of the carboxylate group. Also, the presence of molecules of solvents in crystals results in the formation of interaction networks.

Highlights

The main aim of the search for new drugs is obtaining compounds with appropriate medicinal properties and favorable physical and pharmacological properties, such as good solubility and low toxicity
Fenamic acids belonging to nonsteroidal anti-inflammatory drugs (NSAIDs)3 are commonly used for the treatment of inflammation, pain, and fever
Apart from the fact that the obtained species are hydrogenbonded complexes in which the acidic proton is shifted to the ethacridine nitrogen acceptor, they are solvates with water, methanol, and dimethyl sulfoxide (DMSO) (Table 1): complexes of ethacridine−fenamic acid with water (1a) and methanol (1b) and without solvent (1c crystallized from DMSO), complex of ethacridine−flufenamic acid with water [2], ethacridine−mefenamic acid with water (3a), methanol (3b), and with DMSO (3c), and ethacridine−tolfenamic acid with DMSO [4]

Summary

Introduction

The main aim of the search for new drugs is obtaining compounds with appropriate medicinal properties and favorable physical and pharmacological properties, such as good solubility and low toxicity. Another reason to look for new medicaments is to broaden the spectrum of the therapeutic activity. It is anticipated that complexes of drug substances exhibiting different pharmaceutical properties and medical activities will be characterized by a broader spectrum of action, new therapeutic properties, and better bioavailability of the drug. Many of them exhibit chemopreventive and chemosuppressive effects in different types of cancer.−

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