Structural characterisation, anticancer properties, and BSA binding of 2,6-dipyrazinylpyridines: Insights from experiment and theory

IF 4.7 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Structure Pub Date : 2025-10-03 DOI:10.1016/j.molstruc.2025.144225

Sreenivasulu Enumula , Javed Shaikh , Amin Shaikh , Kounsar N. Sheikh , Pranav Tambe , Dipali N. Lande , Shridhar P. Gejji , Parth Shaligram , Rajesh Gonnade , Mohan Bhadbhade , Khursheed Ahmed

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Abstract

The phenyl-(2,6-di-2-pyrazinyl)pyridine derivatives (L1, L2) were synthesized using a one-pot Krohnke-type method, starting from 2-acetylpyrazine and substituted benzaldehydes. Their structures were characterized using a combination of spectroscopic (NMR, HRMS) and single-crystal X-ray diffraction techniques, complemented by density functional theory (DFT). Single-crystal X-ray diffraction reveals that L1 crystallizes in the C2/c space group (T = 296 K) with its supramolecular assembly being stabilized by C–H⋯N and π–π stacking interactions, whereas L2 facilitates C–H⋯N, N–H⋯π bifurcated, and π–π* interactions. The bio-interaction properties of L1 were studied using fluorescence spectroscopy with bovine serum albumin (BSA) as a model protein. Fluorescence studies demonstrated L1 induces static quenching of BSA, with a binding constant of 5.15 × 10⁴ mol·dm⁻³. Synchronous and three-dimensional fluorescence spectra further demonstrated that L1 brings forth significant conformational changes in BSA. The compounds were evaluated for cytotoxicity against the HCT-116 human colorectal cancer cell line.

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2,6-二吡嗪基吡啶的结构表征、抗癌特性和BSA结合：来自实验和理论的见解

以2-乙酰吡嗪和取代苯甲醛为原料，采用一锅式krohnke法合成了苯基（2,6-二-2-吡嗪基）吡啶衍生物（L1, L2）。利用核磁共振、HRMS和单晶x射线衍射技术，结合密度泛函理论（DFT）对其结构进行了表征。单晶x射线衍射表明，L1在C2/c空间群（T = 296 K）中结晶，其超分子组装被c - h⋯N和π -π堆叠相互作用稳定，而L2促进c - h⋯N， N - h⋯π分叉和π -π *相互作用。以牛血清白蛋白（BSA）为模型蛋白，采用荧光光谱法研究L1的生物相互作用特性。荧光研究表明L1诱导BSA的静态猝灭，其结合常数为5.15 × 10⁴mol·dm⁻³。同步荧光光谱和三维荧光光谱进一步表明，L1引起了牛血清白蛋白明显的构象变化。评价了化合物对HCT-116人结直肠癌细胞系的细胞毒性。

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来源期刊

Journal of Molecular Structure 化学-物理化学

CiteScore

7.10

自引率

15.80%

发文量

2384

审稿时长

45 days

期刊介绍： The Journal of Molecular Structure is dedicated to the publication of full-length articles and review papers, providing important new structural information on all types of chemical species including: • Stable and unstable molecules in all types of environments (vapour, molecular beam, liquid, solution, liquid crystal, solid state, matrix-isolated, surface-absorbed etc.) • Chemical intermediates • Molecules in excited states • Biological molecules • Polymers. The methods used may include any combination of spectroscopic and non-spectroscopic techniques, for example: • Infrared spectroscopy (mid, far, near) • Raman spectroscopy and non-linear Raman methods (CARS, etc.) • Electronic absorption spectroscopy • Optical rotatory dispersion and circular dichroism • Fluorescence and phosphorescence techniques • Electron spectroscopies (PES, XPS), EXAFS, etc. • Microwave spectroscopy • Electron diffraction • NMR and ESR spectroscopies • Mössbauer spectroscopy • X-ray crystallography • Charge Density Analyses • Computational Studies (supplementing experimental methods) We encourage publications combining theoretical and experimental approaches. The structural insights gained by the studies should be correlated with the properties, activity and/ or reactivity of the molecule under investigation and the relevance of this molecule and its implications should be discussed.