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

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.