Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt.
Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt.
Pharmacol Rep. 2021 Jun;73(3):891-906. doi: 10.1007/s43440-020-00193-0. Epub 2021 Jan 3.
Quinolones are well known antibacterial chemotherapeutics. Furthermore, they were reported for other activities such as anticancer and urease inhibitory potential. Modification at C7 of quinolones can direct these compounds preferentially toward target molecules.
Different derivatives of ciprofloxacin by functionalization at the piperazinyl N-4 position with arylidenehydrazinecarbonyl and saturated heterocyclic-carbonyl moieties have been synthesized and characterized using different spectral and analytical techniques. The synthesized compounds were evaluated for anticancer, antibacterial, and urease inhibitory activities.
Among the synthesized compounds derivatives 3f and 3g experienced a potent antiproliferative activity against the breast cancer BT-549 cell line, recording growth percentages of 28.68% and 6.18%, respectively. Additionally, compound 3g revealed a remarkable antitumor potential toward the colon cancer HCT-116 cells (growth percentage 14.76%). Activity of compounds 3f and 3g against BT-549 cells was comparable to doxorubicin (IC = 1.84, 9.83, and 1.29 µM, respectively). Test compounds were less active than their parent drug, ciprofloxacin toward Klebsiella pneumoniae and Proteus mirabilis. However, derivative 4a showed activity better than chloramphenicol against Klebsiella pneumoniae (MIC = 100.64 and 217.08 µM, respectively). Meanwhile, many of the synthesized compounds revealed a urease inhibitory activity greater than their parent. Compound 3i was the most potent urease inhibitor with IC of 58.92 µM, greater than ciprofloxacin and standard inhibitor, thiourea (IC = 94.32 and 78.89 µM, respectively).
This study provided promising derivatives as lead compounds for development of anticancer agents against breast and colon cancers, and others for optimization of urease inhibitors.
喹诺酮类是众所周知的抗菌化学治疗药物。此外，它们还具有其他活性，如抗癌和抑制脲酶的潜力。喹诺酮类在 C7 位的修饰可以使这些化合物更倾向于靶向分子。
用芳基亚腙羰基和饱和杂环羰基取代哌嗪基 N-4 位，合成了不同的环丙沙星衍生物，并通过不同的光谱和分析技术进行了表征。合成的化合物进行了抗癌、抗菌和脲酶抑制活性评价。
在所合成的化合物衍生物中，化合物 3f 和 3g 对乳腺癌 BT-549 细胞系表现出很强的增殖抑制活性，其生长百分比分别为 28.68%和 6.18%。此外，化合物 3g 对结肠癌 HCT-116 细胞表现出显著的抗肿瘤潜力（生长百分比为 14.76%）。化合物 3f 和 3g 对 BT-549 细胞的活性与多柔比星（IC = 1.84、9.83 和 1.29µM）相当。与环丙沙星相比，测试化合物对肺炎克雷伯菌和奇异变形杆菌的活性较弱。然而，衍生物 4a 对肺炎克雷伯菌的活性优于氯霉素（MIC = 100.64 和 217.08µM）。同时，许多合成化合物表现出比母体更强的脲酶抑制活性。化合物 3i 是最有效的脲酶抑制剂，IC 为 58.92µM，大于环丙沙星和标准抑制剂硫脲（IC = 94.32 和 78.89µM）。
本研究提供了有前途的衍生物，可作为开发针对乳腺癌和结肠癌等癌症的抗癌药物的先导化合物，以及其他优化脲酶抑制剂的先导化合物。
