New (S)-verbenone-isoxazoline-1,3,4-thiadiazole hybrids: synthesis, anticancer activity and apoptosis-inducing effect

Background: This study aimed to develop novel isoxazoline-1,3,4-thiadiazole hybrids from (S)-verbenone for potential anticancer treatment, particularly focusing on cytotoxic and apoptotic effects in hormonesensitive MCF-7 and triple-negative MDA-MB-231 breast cancer cells. Methods & results: (S)-verbenone was used to synthesize hybrids through 1,3-dipolar cycloaddition, followed by thorough characterization. The compounds were screened across cancer cell lines, showing significant anticancer effects. Compound 8b notably induced apoptosis via the caspase-3/7 pathway and cell cycle arrest, displaying noteworthy cytotoxicity against MCF-7 and MDA-MB-231 cells. Conclusion: These findings underscore the potential of (S)-verbenone isoxazoline-1,3,4-thiadiazole derivatives for breast cancer therapy due to their remarkable apoptotic activity. This study highlights a promising avenue for advancing breast cancer treatment using these derivatives, founded on (S)-verbenone, showcasing their distinct potential for inducing apoptosis.

背景：本研究旨在以(S)-马鞭烯酮[(S)-verbenone]为起始原料，开发新型异恶唑啉-1,3,4-噻二唑杂合物，用于潜在抗癌治疗，重点考察其对激素敏感型MCF-7细胞与三阴性MDA-MB-231乳腺癌细胞的细胞毒性及凋亡诱导效应。方法与结果：本研究通过1,3-偶极环加成反应，以(S)-马鞭烯酮为起始原料合成目标杂合物，并对其进行了全面的结构表征。随后对所得化合物开展癌细胞系筛选实验，结果显示其具备显著的抗癌活性。其中化合物8b可通过半胱天冬酶(caspase)-3/7通路显著诱导细胞凋亡，并引发细胞周期阻滞，对MCF-7与MDA-MB-231细胞展现出突出的细胞毒性。结论：本研究结果表明，基于(S)-马鞭烯酮的异恶唑啉-1,3,4-噻二唑衍生物因具备优异的凋亡诱导活性，在乳腺癌治疗领域具有潜在应用价值。本研究为基于(S)-马鞭烯酮的乳腺癌治疗研究开辟了极具前景的新方向，凸显了此类衍生物在诱导细胞凋亡方面的独特潜力。