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Synthesis, Biological Evaluation, Molecular Docking, and Molecular Dynamic Simulation Studies of Some New 5-(3,4,5-Trimethoxybenzyl)pyrimidine-2,4-diamine (Trimethoprim) Derivatives via Modified Mannich-Type Reaction

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Abstract

Objective: This article is focused on synthesis and characterisation of 1,1-(((5-(3,4,5triethoxybenzyl)pyrimidine-2,4-diyl))bis(azanediyl))bis(substituted phenyl methylene))bis(naphthalen-2-ol) moieties and evaluated for antibacterial and antioxidant activities as well as molecular docking and molecular dynamic simulation investigations. Methods: In this article we conducted one-pot three component reactions through Betti type reaction. Agar diffusion method was used to evaluate anti-bacterial properties. The DPPH method was used to determine antioxidant activity results. Results: A series of 1,1-(((5-(3,4,5triethoxybenzyl)-pyrimidine-2,4-diyl))bis(azanediyl))bis(substituted phenyl methylene))bis(naphthalen-2-ol) were synthesized via Betti type reaction and evaluated for their antibacterial and antioxidant activities. Further, all the synthesized compounds were characterized by FT-IR, 1H, and 13C NMR, and mass spectral analysis. Discussion: Molecular docking was carried out to study possible potential binding interaction of synthesized Betti base derivatives with 1NC6 PDB as receptor. The molecular dynamic (MD) was performed to investigate stability of binding interaction of drug-target (protein–ligand) complex. All the synthesized compounds were investigated for their antibacterial and antioxidant activity. Conclusions: Betti base derivatives were synthesized and studied on the basis of computer aided drug design including docking and molecular dynamic (MD) simulations and pharmacologically assessed for antioxidant and antibacterial activity. Molecular docking investigation revealed that compounds showed better binding energies in the range –4.1 to –7.3 kcal/mol suggests that the binding occurs efficiently in the receptor–ligand complex. These Betti base derivatives were synthesized via Betti base protocol at 70oC through one-pot three component reaction with acceptable yields, as cost efficient, high yield, easy workup and environmental friendliness. Afterwards, obtained molecules have characterized by FT-IR, NMR, and Mass spectra which confirms the chemical structure of the synthesized compounds.

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DATA AVAILABILITY

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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ACKNOWLEDGMENTS

The authors would like to thank the Chairman of Department of Industrial Chemistry at Kuvempu University in Shankaraghatta for providing laboratory facilities, as well as the University of Mysore and Mangalore for providing spectral data.

Funding

This work was supported by Sc/St cell Kuvempu University, Shankaraghatta, Shimoga, and no, additional grants were obtained.

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Authors and Affiliations

  1. Department of P.G. Studies and Research in Industrial Chemistry, Jnana Sahyadri, Kuvempu University Shankaraghatta, Shivamogga, 577451, Karnataka, India

    Pavithra, Itte Pushpavathi & T. H. Maruthi Nayaka

  2. Department of P.G Studies and Research in Chemistry/Industrial Chemistry, Vijayanagara Sri Krishnadevaraya University, Ballary, 583105, Karnataka, India

    Kuntewale Mohiyouddin Mussuvir Pasha

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Correspondence to Itte Pushpavathi.

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Pavithra, Pushpavathi, I., Pasha, K.M.M. et al. Synthesis, Biological Evaluation, Molecular Docking, and Molecular Dynamic Simulation Studies of Some New 5-(3,4,5-Trimethoxybenzyl)pyrimidine-2,4-diamine (Trimethoprim) Derivatives via Modified Mannich-Type Reaction. Russ J Bioorg Chem 50, 485–499 (2024). https://doi.org/10.1134/S1068162024020079

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