Synthesis of novel ester derivatives via transesterification catalyzed by NaF@CRA: Antiparasitic activity using molecular docking simulations

Abstract

• CRA , NaF@CRA were investigated as a potential heterogeneous ecofriendly catalyst. • CRA, NaF@CRA were characterized by FTIR , XRD, SEM/EDS techniques. • Benzimidazoles analogous were identified by FTIR, NMR , and Es + . • Molecular docking approaches revealed the potential antiviral activity of the synthesized compounds against anti-parasitic activity. • Synthetized compounds (2a, 2b, 2c, and 2d) exhibited significantly higher binding energies compared to the antiviral drug Flubendazole . This study describes the synthesis of novel ester derivatives via transesterification, achieved by condensing benzimidazole analogs with benzyl chloroformate under reflux conditions. A solid catalyst made from calcined red algae (CRA) doped with sodium fluoride (NaF@CRA) was used, yielding products in the range of 81 % to 93 % under optimized conditions. The NaF@CRA catalyst was characterized using various analytical techniques, including X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and Fourier transform infrared spectroscopy (FTIR). It demonstrated excellent stability, maintaining high efficiency after three consecutive cycles. The reaction kinetics and solvent effects were carefully studied, leading to the proposal of a plausible reaction mechanism. The synthesized ester derivatives were characterized by NMR (¹H and ¹³C), mass spectrometry, and FTIR. Molecular docking studies revealed promising antiparasitic potential for these compounds. Specifically, derivatives 2a and 2c showed a binding energy of -9.6 kJ/mol, comparable to the reference drug Flubendazole . Derivatives 2b and 2d exhibited binding energies of -10.1 kJ/mol and -10.2 kJ/mol, respectively, also close to that of Flubendazole. ADME (absorption, distribution, metabolism, and excretion) analysis confirmed favorable pharmacokinetic properties for the synthesized compounds, suggesting their potential as new antiparasitic agents. These findings highlight the efficiency of the proposed methodology and its relevance for therapeutic research.