Synthesis characterization and therapeutic profiling of functionalized 1 7 diaryl heptanoids and their metal chelates for anticancer anti inflammatory antidiabetic and antimicrobial properties

Abstract

his study explored the design, synthesis, and evaluation of nine curcumin analogues and their Cu(II) and Zn(II) metal complexes for therapeutic applications against cancer, diabetes, inflammation, and microbial infections. It employed a multidisciplinary approach integrating chemistry, pharmacology, and computational biology, combining molecular docking, dynamics simulations, and ADME-Tox predictions with in vitro and in vivo experiments. The curcumin analogues, synthesized via Pabon’s method, were structurally modified to enhance pharmacokinetic and pharmacodynamic properties. Spectral characterization confirmed their structures, while virtual screening identified promising candidates with strong bioactivity and minimal toxicity. Zn(II) and Cu(II) complexes exhibited improved stability and solubility, with Zn(II) complexes generally outperforming Cu(II) complexes in bioactivity and safety. Key findings included the strong anticancer potential of NLH, particularly its Zn(II) complex (Zn(NLH)2), against breast cancer targets BRCA1 and TP53. NLE, NLD, and NLF demonstrated high anti-inflammatory activity, while NLB, NLH, and NLE were effective against diabetes-related targets. Zn(II) complexes like Zn(NLE)2 and Zn(NLD)2 were notably potent, showing superior efficacy and reduced cytotoxicity. Antimicrobial studies revealed that NLE and NLD, along with their Zn(II) and Cu(II) complexes, demonstrated strong antibacterial activity against both Gram-positive and Gram-negative bacteria, as well as significant antifungal properties, particularly against Candida albicans. The research successfully synthesized and characterized nine curcumin analogues and their Cu(II) and Zn(II) complexes, demonstrating their potential as multi-functional therapeutic agents. The research confirmed the therapeutic potential of curcumin analogues along with their copper and zinc complexes. The Zn(II) complexes were generally more effective and safer, making them more suitable for further drug development. The alignment of in silico findings with in vitro and in vivo data substantiated the promising bioactivity of these compounds. The study highlighted the potential of these compounds in the development of advanced multi-target drugs with minimized side effects. Future research should optimize bioactivity, extend docking to metal complexes, employ advanced simulations, conduct biochemical and in vivo studies, explore synergistic therapies, and use nano-synthesis to refine curcumin analogues for drug development.