Pradhan Gandhar, Juvale Kapil
Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai, India.
Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai, India.
Bioorg Chem. 2025 Jan;154:107975. doi: 10.1016/j.bioorg.2024.107975. Epub 2024 Nov 19.
Cancer remains one of the leading causes of mortality worldwide, necessitating the continuous search for novel therapeutic agents. Spirooxindole derivatives have recently emerged as a class of compounds with significant potential for cancer treatment owing to their diverse pharmacological activities and unique structural features. The structural diversity of spirooxindole derivatives enables a wide range of modifications, facilitating optimization of their pharmacokinetic and pharmacodynamic properties. Moreover, their ability to interact with multiple molecular targets involved in cancer progression, including kinases, receptors, and enzymes, makes them attractive candidates for multi-targeted therapy. In preclinical studies, numerous spirooxindole derivatives have demonstrated promising antiproliferative activity against various cancer cell lines, including breast, lung, colon, and prostate cancers. Mechanistic investigations have revealed their ability to induce cell cycle arrest and apoptosis and inhibit angiogenesis and metastasis, underscoring their potential as effective anticancer agents. However, challenges such as off-target effects, drug resistance, and limited bioavailability need to be addressed to maximize the therapeutic potential of these compounds. Continued research efforts to elucidate their molecular mechanisms, optimize their pharmacological properties, and conduct rigorous clinical evaluations are warranted to harness their full therapeutic benefits for cancer treatment. This review provides a comprehensive overview of recent advancements in developing spirooxindole derivatives as anticancer agents with structure-activity relationships.
癌症仍然是全球主要的死亡原因之一,因此需要不断寻找新型治疗药物。螺环氧化吲哚衍生物最近作为一类具有显著癌症治疗潜力的化合物出现,这归因于它们多样的药理活性和独特的结构特征。螺环氧化吲哚衍生物的结构多样性使得能够进行广泛的修饰,有助于优化其药代动力学和药效学性质。此外,它们与参与癌症进展的多个分子靶点(包括激酶、受体和酶)相互作用的能力,使其成为多靶点治疗的有吸引力的候选药物。在临床前研究中,许多螺环氧化吲哚衍生物已对包括乳腺癌、肺癌、结肠癌和前列腺癌在内的各种癌细胞系显示出有前景的抗增殖活性。机制研究揭示了它们诱导细胞周期停滞和凋亡以及抑制血管生成和转移的能力,突出了它们作为有效抗癌药物的潜力。然而,需要解决诸如脱靶效应、耐药性和有限的生物利用度等挑战,以最大化这些化合物的治疗潜力。继续进行研究以阐明其分子机制、优化其药理性质并进行严格的临床评估,对于利用它们在癌症治疗中的全部治疗益处是必要的。本综述全面概述了开发螺环氧化吲哚衍生物作为具有构效关系的抗癌药物的最新进展。