Abumansour Hamza, Abusara Osama H, Abu-Sini Mohammad, Khalil Wiam, Ibrahim Ali I M, Badawoud Amal M, Al Yami Majed S, Abulebdah Dina H, Halloush Shiraz
Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan.
Department of Pharmacology, School of Medicine, The University of Jordan, Amman, Jordan.
PLoS One. 2025 Jun 9;20(6):e0324930. doi: 10.1371/journal.pone.0324930. eCollection 2025.
Fluoroquinolones, such as levofloxacin (LVX), are extended-spectrum drugs used for the treatment of bacterial infections. Several fluoroquinolone derivatives have shown promising antibacterial and anticancer activities. Our group has earlier synthesized and investigated thionated LVX analogs, compounds 2 and 3, on A549 (non-small cell lung cancer) cell line and showed promising anticancer activity. The mechanism of cytotoxicity may be, in part, via aldehyde dehydrogenase enzyme inhibition and antioxidation. In this study, compounds 2 and 3 were evaluated on prostate (PC-3), breast (MCF7), colorectal (Caco-2), and small cell lung cancer (H69 and H69AR) cell lines.
The anticancer activity was measured using resazurin colorimetric method. Combination treatments with doxorubicin (DOX) were also employed and combination index (CI) value were calculated.
Compound 3 possessed higher anticancer activity compared to compound 2 on the tested cancer cell lines. Compound 3 had the highest activity on PC-3 cells with IC50 value of 3.58 µM. DOX was also tested for comparison and had IC50 value of less than 0.5 µM in all tested cell lines except for H69AR (DOX-resistant form of H69), which was 4.62 µM. Combination treatment with DOX resulted in significant reduction of cell viability in PC-3, H69, and H69AR cells, with those on H69 and H69AR cells resulted in additive (CI = 1.0) and synergistic effects (CI = 0.6), respectively.
Compound 3, a thionated LVX derivative, showed a promising anticancer activity, prompting its potential repurposing for cancer treatment as well as combination treatment with DOX on DOX-resistant cancer cells.
氟喹诺酮类药物，如左氧氟沙星（LVX），是用于治疗细菌感染的广谱药物。几种氟喹诺酮衍生物已显示出有前景的抗菌和抗癌活性。我们小组 earlier 合成并研究了硫代 LVX 类似物，化合物 2 和 3，在 A549（非小细胞肺癌）细胞系上，并显示出有前景的抗癌活性。细胞毒性机制可能部分是通过醛脱氢酶抑制和抗氧化作用。在本研究中，对化合物 2 和 3 在前列腺（PC - 3）、乳腺（MCF7）、结肠（Caco - 2）和小细胞肺癌（H69 和 H69AR）细胞系上进行了评估。
使用刃天青比色法测量抗癌活性。还采用了与阿霉素（DOX）的联合治疗，并计算联合指数（CI）值。
在测试的癌细胞系上，化合物 3 比化合物 2 具有更高的抗癌活性。化合物 3 在 PC - 3 细胞上具有最高活性，IC50 值为 3.58 μM。还测试了 DOX 进行比较，除了 H69AR（H69 的耐药形式）的 IC50 值为 4.62 μM 外，在所有测试细胞系中其 IC50 值均小于 0.5 μM。与 DOX 的联合治疗导致 PC - 3、H69 和 H69AR 细胞的细胞活力显著降低，其中对 H69 和 H69AR 细胞的联合治疗分别导致相加（CI = 1.0）和协同作用（CI = 0.6）。
化合物 3，一种硫代 LVX 衍生物，显示出有前景的抗癌活性，促使其有可能重新用于癌症治疗以及与 DOX 联合治疗耐药癌细胞。
