Synthesis of some novel coumarin isoxazol sulfonamide hybrid compounds, 3D-QSAR studies, and antibacterial evaluation

Sheida Nasr Esfahani,Azhar Salari-Jazi,Zahrasadat Nazifi,Parisa Sadeghi,Ahmad Reza Massah,Mohammad Sadegh Damavandi

doi:10.1038/s41598-021-99618-w

Abstract

With the progressive and ever-increasing antibacterial resistance pathway, the need for novel antibiotic design becomes critical. Sulfonamides are one of the more effective antibiotics against bacteria. In this work, several novel sulfonamide hybrids including coumarin and isoxazole group were synthesized in five steps starting from coumarin-3-carboxylic acid and 3-amino-5-methyl isoxazole and assayed for antibacterial activity. The samples were obtained in good to high yield and characterized by FT-IR, 13C-NMR, 1H-NMR, CHN and melting point techniques. 3D-QSAR is a fast, easy, cost-effective, and high throughput screening method to predict the effect of the compound's efficacy, which notably decreases the needed price for experimental drug assay. The 3D-QSAR model displayed acceptable predictive and descriptive capability to find r2 and q2 the pMIC of the designed compound. Key descriptors, which robustly depend on antibacterial activity, perhaps were explained by this method. According to this model, among the synthesized sulfonamide hybrids, 9b and 9f had the highest effect on the gram-negative and gram-positive bacteria based on the pMIC. The 3D-QSAR results were confirmed in the experimental assays, demonstrating that our model is useful for developing new antibacterial agents. The work proposes a computationally-driven strategy for designing and discovering new sulfonamide scaffold for bacterial inhibition.

Highlights

With the progressive and ever-increasing antibacterial resistance pathway, the need for novel antibiotic design becomes critical
The antibacterial resistances which were exacerbated by the use and abuse of antibiotics, have become a significant primary public concern
There are some bacterial reports that are resistant to antimicrobial agents and many times these bacteria are MDR or XDR and PDR, antibacterial drugs have been losing their efficacy against infections[1]

Summary

Introduction

With the progressive and ever-increasing antibacterial resistance pathway, the need for novel antibiotic design becomes critical. Key descriptors, which robustly depend on antibacterial activity, perhaps were explained by this method According to this model, among the synthesized sulfonamide hybrids, 9b and 9f had the highest effect on the gram-negative and gram-positive bacteria based on the pMIC. Sulfonamides are Dihydropteroate synthase inhibitors that have been broadly performed to treat bacterial infections These agents contend with aminobenzoic acid and block the nucleic acids and proteins syntheses, so inhibit the microorganism’s g rows[2]. Sulfonamides have drawn far too much attention due to their other medicinal application such as a nticonvulsants[3], protease inhibitors[4], anti-inflammatory5, antitumor[6] and anticancer agents[7] These reasons have prompted numerous attempts to design and synthesize new structural sulfonamides derivatives with exceptional, extended-spectrum and low toxic activity. Several compounds derived from isoxazole exhibited biological activity such as a ntibacterial17,18, anticancer[19], anti-inflammatory20, antipsychotic21, pesticides[22] and anti-rheumatic[23]

Methods

Results

Conclusion