We evaluated the antimicrobial activity of thirty-one nitrogen-containing 5-alpha-androstane derivatives in silico using computer program PASS (Prediction of Activity Spectra for Substances) and freely available PASS-based web applications (www.way2drug.com). Antibacterial activity was predicted for 27 out of 31 molecules; antifungal activity was predicted for 25 out of 31 compounds. The results of experiments, which we conducted to study the antimicrobial activity, are in agreement with the predictions. All compounds were found to be active with MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values in the range of 0.0005-0.6 mg/mL. The activity of all studied 5-alpha-androstane derivatives exceeded or was equal to those of Streptomycin and, except for the 3β-hydroxy-17α-aza-d-homo-5α-androstane-17-one, all molecules were more active than Ampicillin. Activity against the resistant strains of E. coli, P. aeruginosa, and methicillin-resistant Staphylococcus aureus was also shown in experiments. Antifungal activity was determined with MIC and MFC (Minimum Fungicidal Concentration) values varying from 0.007 to 0.6 mg/mL. Most of the compounds were found to be more potent than the reference drugs Bifonazole and Ketoconazole. According to the results of docking studies, the putative targets for antibacterial and antifungal activity are UDP-N-acetylenolpyruvoylglucosamine reductase and 14-alpha demethylase, respectively. In silico assessments of the acute rodent toxicity and cytotoxicity obtained using GUSAR (General Unrestricted Structure-Activity Relationships) and CLC-Pred (Cell Line Cytotoxicity Predictor) web-services were low for the majority of compounds under study, which contributes to the chances for those compounds to advance in the development.

中文翻译：

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含氮5-α-雄甾烷衍生物的抗菌活性：计算机和实验研究。

我们使用计算机程序PASS（物质的活性谱预测）和可免费获得的基于PASS的Web应用程序（www.way2drug.com），评估了三十一种含氮的5-α-雄烷衍生物在计算机上的抗菌活性。预测31种分子中有27种具有抗菌活性。预测31种化合物中有25种具有抗真菌活性。我们进行的研究抗菌活性的实验结果与预测相符。发现所有化合物都具有0.0005-0.6 mg / mL的MIC（最小抑菌浓度）和MBC（最小杀菌浓度）值。所有研究的5-α-雄甾烷衍生物的活性均超过或等于链霉素的活性，除了3β-羟基-17α-氮杂-d-homo-5α-雄甾烷-17-一个，所有分子都比氨苄西林更具活性。实验中还显示了针对大肠杆菌，铜绿假单胞菌和耐甲氧西林金黄色葡萄球菌的耐药菌株的活性。用0.007至0.6 mg / mL的MIC和MFC（最小杀真菌浓度）值确定抗真菌活性。发现大多数化合物比参考药物联苯苄唑和酮康唑更有效。根据对接研究的结果，抗菌和抗真菌活性的推定目标分别是UDP-N-乙炔基丙酮酸丙酮酰葡萄糖胺还原酶和14-α脱甲基酶。