Paringamalai Noorudeen, Ameen Syed Tajudeen Syed, Ibrahim Abdul Matheen, Taju Gani, Majeed Seepoo Abdul, Hameed Azeez Sait Sahul, Mithra Sivaraj, Imran Predhanekar Mohamed, Kubaib Attar
PG and Research Department of Chemistry, C. Abdul Hakeem College (Autonomous), Affiliated to Thiruvalluvar University, Ranipet District, Melvisharam, 632 509, Tamil Nadu, India.
Aquatic Animal Health Laboratory, PG and Research Department of Zoology, C. Abdul Hakeem College (Autonomous), Affiliated to Thiruvalluvar University, Melvisharam, 632 509, Ranipet District, Tamil Nadu, India.
In Vitro Cell Dev Biol Anim. 2025 Jun 19. doi: 10.1007/s11626-025-01062-x.
The skin is a vital organ that regulates the temperature, nutrient absorption, and perception of sensations. Wound healing is a complex biological process in multicellular systems that consists of four key phases: hemostasis, inflammation, proliferation, and remodeling. This study develops a new approach for synthesizing dihydropyrimidinones (DHPM) named Biginelli scaffolds via a simple, rapid, eco-friendly, and cost-effective solvent-free Biginelli reaction for wound healing activities. The synthesis involved a one-pot three-component coupling reaction of β-ketoester derivatives, anisaldehyde, and simple urea in a domestic microwave oven. The synthesized (B1-B4) scaffolds were characterized using melting point, UV-Vis, FT-IR, HRMS, 2D-NMR (NOESY), and proton/carbon NMR spectroscopies. The molecular docking results showed that the synthetic scaffolds (B1-B4) had strong binding abilities, with B3 and B4 having the best interactions in the group, similar to the control compound (curcumin). It exhibited less cytotoxic effects up to 80 µg/mL in Tilapia gill (TG) cells in the MTT assay. The synthesized scaffolds (60 µg/mL) enhanced TG cell growth and had potential applications in wound healing. Biginelli (B1-B4) scaffolds showed good antioxidant properties in the DPPH assay. RT-qPCR analysis indicated that TG cells exposed to different (B1-B4) scaffold concentrations had significantly increased VEGF gene expression. The scaffolds showed no toxic effects on adsorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis, and the structure was optimized using the DFT-B3LYP-6311G-(d,p) hybrid basis set. This method has wide applications in future research and provides insights into tissue engineering and biomedical applications.
皮肤是调节体温、营养吸收和感觉感知的重要器官。伤口愈合是多细胞系统中的一个复杂生物学过程，包括四个关键阶段：止血、炎症、增殖和重塑。本研究开发了一种通过简单、快速、环保且经济高效的无溶剂Biginelli反应合成二氢嘧啶酮（DHPM）（即Biginelli支架）的新方法，用于伤口愈合活性研究。该合成涉及β-酮酯衍生物、茴香醛和简单尿素在家用微波炉中的一锅三组分偶联反应。使用熔点、紫外可见光谱、傅里叶变换红外光谱、高分辨质谱、二维核磁共振（NOESY）以及质子/碳核磁共振光谱对合成的（B1 - B4）支架进行了表征。分子对接结果表明，合成支架（B1 - B4）具有很强的结合能力，其中B3和B4在该组中具有最佳相互作用，类似于对照化合物（姜黄素）。在MTT试验中，其在罗非鱼鳃（TG）细胞中高达80μg/mL时表现出较低的细胞毒性作用。合成支架（60μg/mL）促进了TG细胞生长，在伤口愈合方面具有潜在应用。Biginelli（B1 - B4）支架在DPPH试验中显示出良好的抗氧化性能。实时定量聚合酶链反应分析表明，暴露于不同（B1 - B4）支架浓度的TG细胞中血管内皮生长因子（VEGF）基因表达显著增加。这些支架在吸附、分布、代谢、排泄和毒性（ADMET）分析中未显示出毒性作用，并使用密度泛函理论 - B3LYP - 6 - 311G -（d,p）混合基组对结构进行了优化。该方法在未来研究中有广泛应用，并为组织工程和生物医学应用提供了思路。
