H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, Karachi University, Karachi 74200, Pakistan.
Federal Urdu University of Arts, Science and Technology, Department of Pharmacology, Faculty of Pharmacy, Pakistan.
Bioorg Chem. 2020 Jul;100:103937. doi: 10.1016/j.bioorg.2020.103937. Epub 2020 May 13.
In treating wounds, long lasting infection is considered the major impediment. Drugs are rendered ineffective by pathogenic microorganisms via antibiotic resistance and calls for designing and development of new drugs. Herein, we report synthesis of eight different N-alkylated pyridine-based organic salts QAS 1-8 and their antibacterial, antibiofilm and wound healing activities. 3-(2-R-hydrazinecarbonyl)-1-propylpyridinium Bromide was the parent compound while R group was varying in each salt composed of different aromatic aldehyde moieties. In the antibacterial activity against S. aureus and E. coli, amoxicillin shows IC near to 25 µg/mL inhibiting 58 ± 0.4% S. aureus while ceftriaxone inhibited 55 ± 0.5% E. coli at a concentration of 10 µg/mL. The highest IC (56 ± 0.5% against S. aureus; 55 ± 0.5% against E. coli) was shown by compound QAS 7 at the concentration of 100 µg/mL; followed by the QAS 6 (55 ± 0.5% against E. coli) and QAS 2 (55 ± 0.5% against E. coli). In the antibiofilm activity, QAS 6, QAS 1 and QAS 8 inhibited 58 ± 0.4% S. aureus at a concentration of 75 µg/mL, while QAS 2 inhibited E. coli at the same concentration and amount. QAS 7, 3 and 1 inhibited almost 90% while QAS 6 inhibited 95 ± 1.1%of E. coli at a concentration of 250 µg/mL. Highest MBIC was provided by QAS 7 (52 ± 0.4%) against S. aureus at a concentration of 50 µg/mL that is very near to the standard amoxicillin. Antibacterial and antibiofilm activity results were also supported by the atomic force microscopy (AFM). In the wound healing activity, QAS 8 healed 90.8 ± 4.3% of the wound in 21 days with an average period of epithelialization (POE) of 19 ± 1.4 days; that is far better than povidone iodine ointment (81.5 ± 3.3% of the wound in the 21 days with 22.4 ± 2.9 days of POE). It is concluded from this study that the synthesized compounds QAS 2, 7 and 8 can be used for further mechanistic studies to be employed as antibacterial, antibiofilm and wound healing agents.
在治疗伤口时，持久的感染被认为是主要障碍。致病微生物通过抗生素耐药性使药物失效，因此需要设计和开发新的药物。在此，我们报告了八种不同的 N-烷基吡啶基有机盐 QAS 1-8 的合成及其抗菌、抗生物膜和伤口愈合活性。3-(2-R-肼羰基)-1-丙基吡啶溴化物是母体化合物，而 R 基团在每个盐中都不同，由不同的芳香醛部分组成。在对金黄色葡萄球菌和大肠杆菌的抗菌活性中，阿莫西林的 IC 接近 25 µg/mL，抑制 58 ± 0.4%的金黄色葡萄球菌，而头孢曲松在 10 µg/mL 浓度下抑制 55 ± 0.5%的大肠杆菌。在 100 µg/mL 浓度下，化合物 QAS 7 表现出最高的 IC（对金黄色葡萄球菌为 56 ± 0.5%；对大肠杆菌为 55 ± 0.5%）；其次是 QAS 6（对大肠杆菌为 55 ± 0.5%）和 QAS 2（对大肠杆菌为 55 ± 0.5%）。在抗生物膜活性方面，QAS 6、QAS 1 和 QAS 8 在 75 µg/mL 浓度下抑制 58 ± 0.4%的金黄色葡萄球菌，而 QAS 2 在相同浓度和数量下抑制大肠杆菌。QAS 7、QAS 3 和 QAS 1 几乎抑制了 90%，而 QAS 6 在 250 µg/mL 浓度下抑制了 95 ± 1.1%的大肠杆菌。在 50 µg/mL 浓度下，QAS 7 对金黄色葡萄球菌的 MBIC 最高（52 ± 0.4%），接近标准阿莫西林。抗菌和抗生物膜活性结果也得到原子力显微镜（AFM）的支持。在伤口愈合活性方面，QAS 8 在 21 天内愈合了 90.8 ± 4.3%的伤口，上皮化平均时间（POE）为 19 ± 1.4 天；这远比聚维酮碘软膏（21 天内愈合 81.5 ± 3.3%的伤口，POE 为 22.4 ± 2.9 天）好得多。从这项研究中可以得出结论，合成的化合物 QAS 2、7 和 8 可用于进一步的机制研究，作为抗菌、抗生物膜和伤口愈合剂。
