Structure-Based Designing, Solvent Less Synthesis of 1,2,3,4-Tetrahydropyrimidine-5-carboxylate Derivatives: A Combined In Vitro and In Silico Screening Approach.

Uzma Arshad,Aqsa Hassan,Nusrat Shafiq,Tahir Mehmood,Sibtain Ahmed,Zaheer Ahmad,Naseem Akhtar,Shagufta Parveen

doi:10.3390/molecules26154424

Abstract

Objective: In this study, small molecules possessing tetrahydropyrimidine derivatives have been synthesized having halogenated benzyl derivatives and carboxylate linkage. As previously reported, FDA approved halogenated pyrimidine derivatives prompted us to synthesize novel compounds in order to evaluate their biological potential. Methodology: Eight pyrimidine derivatives have been synthesized from ethyl acetoacetate, secondary amine, aromatic benzaldehyde by adding catalytic amount of CuCl2·2H2O via solvent less Grindstone multicomponent reagent method. Molecular structure reactivity and virtual screening were performed to check their biological efficacy as an anti-oxidant, anti-cancer and anti-diabetic agent. These studies were supported by in vitro analysis and QSAR studies. Results: After combined experimental and virtual screening 5c, 5g and 5e could serve as lead compounds, having low IC50 and high binding affinity.

Highlights

IntroductionHeterocyclic compound chemistry has revolutionized the modern and versatile medicinal chemistry [1]
All the compounds 5a–h was evaluated for their biological potential against diabetes, radical scavenge and cancer cell lines
After combinatorial in vitro and in silico analysis, compound 5c was pharmacologically active for anti-oxidant activity, 5e and 5c for cytotoxicity and 5g for combating diabetes

Summary

Introduction

Heterocyclic compound chemistry has revolutionized the modern and versatile medicinal chemistry [1] These heterocyclic compounds have a very expansive effect on human life and influence heterogeneous fields like medicine, polymer science, agronomy and various chemical industries [2]. DHPMs mode of action is evident from the formation of H-bonding along with nucleotides like uracil, thymine, cytosine, adenine and guanine in both DNA and RNA [4] This class of heterocyclic synthetic compounds contains many naturally occurring therapeutic drugs like quinine, emetine, dibucaine, morphine and reserpine, as shown in Figure 1 [5,6]

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