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A series of novel ciprofloxacin (CP) derivatives substituted at the N-4 position with biologically active moieties were designed and synthesised. 14 compounds were 1.02- to 8.66-fold more potent than doxorubicin against T-24 cancer cells. Ten compounds were 1.2- to 7.1-fold more potent than doxorubicin against PC-3 cancer cells. The most potent compounds 6, 7a, 7b, 8a, 9a, and 10c showed significant Topo II inhibitory activity (83–90% at 100 μM concentration). Compounds 6, 8a, and 10c were 1.01- to 2.32-fold more potent than doxorubicin. Compounds 6 and 8a induced apoptosis in T-24 (16.8- and 20.1-fold, respectively compared to control). This evidence was supported by an increase in the level of apoptotic caspase-3 (5.23- and 7.6-fold, sequentially). Both compounds arrested the cell cycle in the S phase in T-24 cancer cells while in PC-3 cancer cells the two compounds arrested the cell cycle in the G1 phase. Molecular docking simulations of compounds 6 and 8a into the Topo II active site rationalised their remarkable Topo II inhibitory activity.

A novel series of benzimidazole derivatives with methoxylated aryl groups was designed and synthesized as molecules with potential cytotoxic activity. In vitro cytotoxic activity over HCT-116 cells showed that N-(benzimidazothiazolone)acetamides 11a, 11b and 11c were found to be the most cytotoxic compounds compared camptothecin (CPT). The tested compounds had a dual topoisomerase I-β (Topo I-β) and tubulin inhibiting activities when compared to CPT and Podophyllotoxin (Podo) where, compounds l0a, l0b, 11a and 11b exhibited a potent inhibitory activity on Topo I-β enzyme in nano-molar concentration, on the other hand, compounds 12b and 13b exhibited the best inhibitory activity β-tubulin polymerization. Results of the cell cycle analysis as well as the results of annexin-V on HCT-116 cells showed that benzimidazothiazoles 12b and 13b had a pro-apoptotic activity higher than CPT by 1.33- and 1.30-folds, respectively. Moreover, the concentration of p53, Bax/Bcl-2 ratio and caspase 3/7 increased in compounds l0b, 11b, l2b, 13b, especially, compounds 11b and 13b exhibited an increased level of these mediators than CPT. Finally, compound 11b regulated the radiosensitizing activity of the HCT-116 cells by modulating the chromosomal instability.