A series of new sulphonamide and carbamate derivatives of Nebivolol drug intermediate (5) were designed and synthesized by reacting various biopotent sulphonylchlorides and chloroformates. The synthesized compounds are structurally characterized by spectral (IR, ¹H & ¹³C NMR and mass) and screened for their in vitro antimicrobial activity against four bacterial and three fungal strains, in vitro and in vivo antiinflammatory activity against LPS-induced inflammation in RAW 264.7, in vitro COX-1 and COX-2 inhibition potentiality, antagonistic profiles of carrageenan induced paw edema and cotton pellet induced granuloma in rat. Further, the compounds were screened for their antimicrobial and antiinflammatory activity against DNA gyrase A, COX-1 and COX-2 by using molecular docking approach. The bioactivity and toxicity risks were analysed through Molecular Operating Environment. The results revealed that the compounds 8b, 8c, 8d, 8e, 8f, 8g and 9a exhibited the most promising antimicrobial activity against all the bacterial and fungal strains tested when compared with the standard drugs streptomycin and fluconazole. In view of in antiinflammatory activity, the compounds, 8b, 8c, 8d, 8e, 8f, 8g and 9a have shown potent antiinflammatory activity by inhibiting the LPS-induced inflammation in RAW 264.7 cell line, concentration dependent inhibition of COX-1 and COX-2, dose response dependent antagonism of carrageenan induced paw edema and granuloma tissue in rat. Molecular docking, ADMET and QSAR studies predicted that the recorded in silico profiles are in strong correlation with in vitro and in vivo antimicrobial and antiinflammatory results. In addition, the elevated toxicology risks of the title compounds are identified with in the potential limits of drug candidates. Hence, it is suggested that the synthesized derivatives will stand as the promising antimicrobial and anti-inflammatory drug candidates in future.

中文翻译：

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奈必洛尔中间体的新系列磺胺和氨基甲酸酯衍生物的设计、合成、表征以及体外、体内和计算机内抗菌和抗炎活性

通过多种生物活性磺酰氯与氯甲酸酯反应，设计合成了一系列新的奈必洛尔药物中间体磺酰胺和氨基甲酸酯衍生物（5 ）。合成的化合物通过光谱（IR、¹ H 和¹³ C NMR 和质量）在结构上进行表征，并筛选它们对四种细菌和三种真菌菌株的体外抗菌活性，以及​​对 RAW 中 LPS 诱导的炎症的体外和体内抗炎活性264.7，体外COX-1 和 COX-2 抑制潜力，角叉菜胶诱导大鼠爪水肿和棉丸诱导大鼠肉芽肿的拮抗作用。此外，通过使用分子对接方法，筛选了这些化合物对 DNA 促旋酶 A、COX-1 和 COX-2 的抗菌和抗炎活性。通过分子操作环境分析生物活性和毒性风险。结果表明，化合物8b、8c、8d、8e、8f、8g和9a与标准药物链霉素和氟康唑相比，对所有测试的细菌和真菌菌株表现出最有希望的抗菌活性。鉴于抗炎活性，化合物8b、8c、8d、8e、8f、8g和9a通过抑制RAW 264.7细胞系中LPS诱导的炎症、COX-1和COX的浓度依赖性抑制而显示出有效的抗炎活性-2、剂量反应依赖性拮抗角叉菜胶诱导的大鼠爪水肿和肉芽肿组织。分子对接、ADMET 和 QSAR 研究预测，计算机记录的图谱与体外和体内抗菌和抗炎结果密切相关。此外，在候选药物的潜在限制中确定了标题化合物的升高的毒理学风险。因此，建议合成的衍生物将成为未来有希望的抗菌和抗炎候选药物。