A new series of 5,7-dibromoquinoline scaffold-based derivatives with varied flexibility substituents at position 8 of the ring system has been synthesized as potential anticancer agents. The new compounds were evaluated for their in vitro antiproliferative activity versus the human breast cancer cell lines MCF-7 and MDA-MB231. Generally, both cell lines were responsive to the cytotoxic effect of the synthesized analogues. Compounds 4a, 5c and 7b were chosen for nanoformulation studies to assess the effect of enhancing their solubility profile on their cytotoxic ability. Indeed, the pluronic nanomicelles of the three formulated derivatives showed an observable significant increase in their cytotoxic efficacy demonstrating a positive impact of the used nanoformulations on the delivery of the active compounds to their cellular biological targets.