A New Family of Benzo[h]Chromene Based Azo Dye: Synthesis, In-Silico and DFT Studies with In Vitro Antimicrobial and Antiproliferative Assessment.

Alaa S Abd-El-Aziz,Mohamed Hagar,Eman Assirey,Rawda M Okasha,Azhaar Alsaggaf,Tarek H Afifi,Arshi Naqvi

doi:10.3390/ijms22062807

Abstract

The high biological activity of the chromene compounds coupled with the intriguing optical features of azo chromophores prompted our desire to construct novel derivatives of chromene incorporating azo moieties 4a-l, which have been prepared via a three-component reaction of 1-naphthalenol-4-[(4-ethoxyphenyl) azo], 1, with the benzaldehyde derivatives and malononitrile. The structural identities of the azo-chromene 4a-l were confirmed on the basis of their spectral data and elemental analysis, and a UV–visible study was performed in a Dimethylformamide (DMF) solution for these molecules. Additionally, the antimicrobial activity was investigated against four human pathogens (Gram-positive and Gram-negative bacteria) and four fungi, employing an agar well diffusion method, with their minimum inhibitory concentrations being reported. Molecules 4a, 4g, and 4h were discovered to be more efficacious against Syncephalastrum racemosum (RCMB 05922) in comparison to the reference drugs, while compounds 4b and 4h demonstrated the highest inhibitory activity against Escherichia coli (E. coli) in evaluation against the reference drugs. Moreover, their cytotoxicity was assessed against three different human cell lines, including human colon carcinoma (HCT-116), human hepatocellular carcinoma (HepG-2), and human breast adenocarcinoma (MCF-7) with a selection of molecules illustrating potency against the HCT-116 and MCF-7 cell lines. Furthermore, the molecular modeling results depicted the binding interactions of the synthesized compounds 3b and 3h in the active site of the E. coli DNA gyrase B enzyme with a clear SAR (structure–activity relationship) analysis. Lastly, the density functional theory’s (DFTs) theoretical calculations were performed to quantify the energy levels of the Frontier Molecular Orbitals (FMOs) and their energy gaps, dipole moments, and molecular electrostatic potentials. These data were utilized in the chemical descriptor estimations to confirm the biological activity.

Highlights

The last century has seen an exponential increase in the growth of cancerous masses and this has emerged as one of the primary global causes of mortality in this age
As an extension of our aforementioned work [41,42,43], we present the synthesis and characterization of the novel azo-chromene molecules and investigate their in vitro antimicrobial activity and cytotoxic effects
In our attempts to synthesize chromene derivatives, the three-component condensation reaction of 1-naphthalenol-4-[(4-ethoxyphenyl) azo] 1 with malononitrile and/or ethyl cyanoacetate 2 and the benzaldehyde containing either electron-donating (EDG) or -withdrawing (EWG) derivatives 3a–l was executed in an ethanolic reflux solution using piperidine and afforded 2-amino-6-(4-ethoxyphenylazo)-4(-phenyl)-4H-benzo[h]chromene3-carbonitrile derivatives in good yield, as illustrated in Scheme 1

Summary

Introduction

The last century has seen an exponential increase in the growth of cancerous masses and this has emerged as one of the primary global causes of mortality in this age. An entire cancer therapeutics industry has been established throughout the years, which is devoted to the research and discovery of novel cancer treatments, which include surgery, radiotherapy, chemotherapy, hormonal therapy, targeted drug therapy, and clinical trials [2]. A suitable candidate of these criteria is the family of chromene molecules, which have captivated cancer researchers for their diversified and assorted medicinal applications, anti-inflammatory, anti-cancer, and anti-fungal [3,4,5,6,7,8,9]. The design and introduction of chromene compounds as innovative medicinal agents has been a central focus in the emerging drug industry. Venugopala and co-workers reported several chromene molecules performed a focal role in the treatment of various cancers either as natural or synthetic compounds [10]. Chromene molecules are deemed ‘privileged medicinal scaffolds’ due to their unique pharmacological and biological activities [5,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26]

Methods

Results

Conclusion