We report the design‐synthesis of several nitrothiophene containing molecules as antituberculosis agents. The molecules were designed on the basis of previously reported nitrofuran molecules in our laboratory, and the α,β‐unsaturated linker was modified to cyclized linker in order to overcome the challenge of low solubility and possible toxicity. The stereo‐electronic properties such as HOMO, LUMO, and HOMO‐LUMO gap along with other properties such as aqueous solvation energies and QPLogS values were studied. The designed molecules were synthesized and tested for in vitro antituberculosis activity, and some molecules were found to be highly active comparable to standard drugs. Further, the aqueous solubility was determined using visual inspection method and the designed molecules were found to be more soluble than their chalcone counterparts. Cytotoxicity studies were performed and the molecules were found to be non‐cytotoxic. Electroanalytical studies proved nitro reduction as the mechanism of action for these molecules. Thus, this study provides potential nitrothiophene containing hits with improved solubility and reduced chances of toxicity.

中文翻译：

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具有改善的溶解度和潜在的抗结核活性的5-（5-硝基噻吩-2-基）-3-苯基-4,5-二氢-1H-吡唑衍生物的设计与合成

我们报告了几种含有硝基噻吩的分子作为抗结核剂的设计合成。这些分子是根据我们实验室中先前报道的硝基呋喃分子设计的，并且将α，β-不饱和连接基修饰为环化连接基，以克服低溶解度和可能的毒性的挑战。研究了诸如HOMO，LUMO和HOMO-LUMO间隙的立体电子性质，以及诸如水合溶剂化能和QPLogS值的其他性质。合成了设计的分子并测试了其体外抗结核活性，发现有些分子具有与标准药物相当的高活性。此外，使用目测方法确定水溶性，并且发现设计的分子比查尔酮对应物更可溶。进行了细胞毒性研究，发现该分子无细胞毒性。电分析研究证明硝基还原是这些分子的作用机理。因此，这项研究提供了潜在的含硝基噻吩的命中物，具有改善的溶解度和降低的毒性机会。