Pharmaceutical Sciences Department, College of Health Sciences, The Public Authority for Applied Education and Training, Adailiyah, Kuwait.
Chemistry Department, Faculty of Science, Kuwait University, Kuwait City, Kuwait.
Bioorg Chem. 2021 Mar;108:104658. doi: 10.1016/j.bioorg.2021.104658. Epub 2021 Jan 21.
Development of new derivatives of commercial antibiotics using different organic reagents and testing these derivatives against different microorganisms are the main goals of this article. Thus, the antibiotic ciprofloxacin, CF, was acylated via reaction with ethyl cyanoacetate and ethyl acetoacetate in basic medium to give the cyanoacetylpiprazinyl dihydroquinoline derivative 3, and oxobutanoylpiprazinyl dihydroquinoline derivative 5, respectively. On the other hand, N-alkylated derivatives 8-10, were prepared through the reaction of CF with chloroacetonitrile, chloroacetyl acetone and chloroacetone in the presence of carbonate salt. In basic medium, both 3 and 10 were coupled with benzenediazonium chloride to afford hydrazono derivatives, which were then cyclized to give 4-(dihydropyridazinecarbonyl)piperazinyl-1,4-dihydroquinoline. Furthermore, compounds 3 and 10 were reacted with benylidenemalononitrile to produce 4H-pyan and pyrido[1,2-a]pyrazine derivatives, respectively. Both 3 and 10 were reacted with DMFDMA to give enaminone derivatives. These enaminones were cyclized to aminopyrimidine derivatives by reacting with urea or thiourea. X-ray, elemental analysis and spectral data were used to illustrate and confirm the structures of the isolated compounds. The bioactivities of the novel compounds were investigated against different gram-positive and gram-negative bacteria. In addition, these novel antibiotic derivatives were tested against ciprofloxacin-resistant bacteria isolated from patients aged 65-74 years. This study reveals that most of the modified drugs show high to moderate antibacterial activity. Additionally, these drugs show good effects against ciprofloxacin-resistant bacteria.
本文主要目标是利用不同的有机试剂开发商业抗生素的新衍生物，并针对不同的微生物测试这些衍生物。因此，通过与氰基乙酸乙酯和乙酰乙酸乙酯在碱性介质中的反应，将抗生素环丙沙星 CF 酰化，分别得到氰乙酰基哌嗪基二氢喹啉衍生物 3 和氧代丁酰基哌嗪基二氢喹啉衍生物 5。另一方面，通过 CF 与氯乙腈、氯乙酰丙酮和氯丙酮在碳酸盐盐存在下的反应，制备 N-烷基化衍生物 8-10。在碱性介质中，3 和 10 与苯重氮氯化物偶联得到腙衍生物，然后环化得到 4-(二氢哒嗪羰基)哌嗪基-1,4-二氢喹啉。此外，化合物 3 和 10 与苯亚甲基丙二腈反应分别产生 4H-吡喃和吡啶并[1,2-a]吡嗪衍生物。3 和 10 均与 DMFDMA 反应得到烯胺酮衍生物。这些烯胺酮通过与尿素或硫脲反应环化得到氨基嘧啶衍生物。X 射线、元素分析和光谱数据用于说明和确认分离化合物的结构。研究了新型化合物对不同革兰氏阳性和革兰氏阴性细菌的生物活性。此外，还测试了这些新型抗生素衍生物对从 65-74 岁患者中分离出的耐环丙沙星细菌的活性。本研究表明，大多数修饰药物具有高至中度的抗菌活性。此外，这些药物对耐环丙沙星的细菌有良好的效果。
