"Spiro-pyrrolizidine-benzyloxy hybrid as synergistic partner to doxorubicin cardio-safe breast cancer chemotherapy".

IF 3.4 4区医学 Q3 CHEMISTRY, MEDICINAL

Future medicinal chemistry Pub Date : 2025-10-11 DOI:10.1080/17568919.2025.2570968

Uthirapathi Rajapandiyan, M Raj Kumar, H Manikandan, K Sivakumar

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引用次数: 0

Abstract

Purpose of objective: This study aims to develop novel spiro-pyrrolizidine-benzyloxy hybrids (RP₁, RP₂, and RP₃) to reduce the dosage and mitigate the side effects of doxorubicin (DOX) while harnessing potential synergistic effects for enhanced anticancer efficacy.

Methods: Spiro-pyrrolizidine-benzyloxy hybrids (RP₁, RP₂, and RP₃) were synthesized using isatin, L-proline, and sub-chalcone. The anticancer potential of these compounds was evaluated against MDA-MB-231 breast cancer cells. Based on superior efficacy, RP₁ was selected and compounded with doxorubicin in different ratios. The anticancer efficacy of these compounded formulations was assessed through cell viability assays and IC50 values.

Results: Among the synthesized hybrids, RP₁ exhibited the highest anticancer efficacy against MDA-MB-231 cells. When RP1 was combined with doxorubicin, the combination showed reduced cell viability, with the most effective ratio being 23.50 µM (20:80) (RP₁: dox), followed by 11.22 µM (50:50) and 8.82 µM (80:20). The compounded formulation resulted in a lower IC50 value compared to doxorubicin alone, indicating enhanced efficacy.

Conclusions: Compounding RP₁ with doxorubicin effectively enhances anticancer activity while potentially reducing the side effects associated with doxorubicin's quinone-hydroquinone moiety. The optimized formulation (80:20) presents a promising approach for improving breast cancer treatment outcomes.

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“螺-吡咯利西汀-苄氧基杂合物作为阿霉素心脏安全乳腺癌化疗的增效伙伴”。

目的：本研究旨在开发新型螺-吡咯利西汀-苯氧基杂合体（RP1、RP2和RP3），以减少阿霉素（DOX）的剂量和副作用，同时利用潜在的协同效应增强其抗癌效果。方法：以isatin、l -脯氨酸和亚查尔酮为原料合成螺-吡咯利西啶-苯氧基杂合体RP1、RP2和RP3。这些化合物对MDA-MB-231乳腺癌细胞的抗癌潜力进行了评估。基于其优越的疗效，选择RP1与阿霉素按不同比例配用。通过细胞活力测定和IC50值评估这些复合制剂的抗癌功效。结果：在合成的杂交种中，RP1对MDA-MB-231细胞的抗癌作用最高。当RP1与阿霉素联合使用时，细胞活力降低，其最有效比值为23.50µM (20:80) (RP1: dox)，其次为11.22µM（50:50）和8.82µM（80:20）。与单独使用阿霉素相比，复合制剂的IC50值较低，表明疗效增强。结论：RP1与阿霉素合用可有效增强抗肿瘤活性，同时可能减少阿霉素醌-对苯二酚部分的副作用。优化的配方（80:20）为改善乳腺癌治疗结果提供了一个有希望的方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Future medicinal chemistry CHEMISTRY, MEDICINAL-

CiteScore

5.80

自引率

2.40%

发文量

118

审稿时长

4-8 weeks

期刊介绍： Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.