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; Sibtain Ahmed; Nusrat Shafiq; Zaheer Ahmad; Aqsa Hassan; Naseem Akhtar; Shagufta Parveen; Tahir Mehmood

doi:10.3390/molecules26154424

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

Molecules. 2021 Jul 22;26(15):4424. doi: 10.3390/molecules26154424.

Authors

Uzma Arshad¹, Sibtain Ahmed², Nusrat Shafiq¹, Zaheer Ahmad³, Aqsa Hassan¹, Naseem Akhtar⁴, Shagufta Parveen¹, Tahir Mehmood⁵

Affiliations

¹ Department of Chemistry, Government College Women University Faisalabad, Faisalabad 38000, Pakistan.
² Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093, USA.
³ Department of Chemistry, University of Wah, Rawalpindi 47000, Pakistan.
⁴ Department of Chemistry, Government Sadiq College Women University, Bahawalpur 63000, Pakistan.
⁵ Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore 54000, Pakistan.

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.

Keywords: DFT; MTT; QSAR; in silico; in vitro; molecular docking; pyrimidine; solvent less.

MeSH terms

Antineoplastic Agents* / chemical synthesis
Antineoplastic Agents* / chemistry
Antineoplastic Agents* / pharmacology
Antioxidants* / chemical synthesis
Antioxidants* / chemistry
Antioxidants* / pharmacology
Drug Screening Assays, Antitumor
Hep G2 Cells
Humans
Hypoglycemic Agents* / chemical synthesis
Hypoglycemic Agents* / chemistry
Hypoglycemic Agents* / pharmacology
Molecular Docking Simulation*
Pyrimidines* / chemical synthesis
Pyrimidines* / chemistry
Pyrimidines* / pharmacology

Substances

Antineoplastic Agents
Antioxidants
Hypoglycemic Agents
Pyrimidines