Kucerova-Chlupacova Marta, Kunes Jiri, Buchta Vladimir, Vejsova Marcela, Opletalova Veronika
Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
Molecules. 2015 Jan 12;20(1):1104-17. doi: 10.3390/molecules20011104.
Infectious diseases, such as tuberculosis and invasive mycoses, represent serious health problems. As a part of our long-term efforts to find new agents for the treatment of these diseases, a new series of pyrazine analogs of chalcones bearing an isopropyl group in position 5 of the pyrazine ring was prepared. The structures of the compounds were corroborated by IR and NMR spectroscopy and their purity confirmed by elemental analysis. The susceptibility of eight fungal strains to the studied compounds was tested. The results have been compared with the activity of some previously reported propyl derivatives. The only strain that was susceptible to the studied compounds was Trichophyton mentagrophytes. It was found that replacing a non-branched propyl with a branched isopropyl did not have a decisive and unequivocal influence on the in vitro antifungal activity against T. mentagrophytes. In vitro activity against Trichophyton mentagrophytes comparable with that of fluconazole was exhibited by nitro-substituted derivatives. Unfortunately, no compound exhibited efficacy comparable with that of terbinafine, which is the most widely used agent for treating mycoses caused by dermatophytes. Some of the prepared compounds were assayed for antimycobacterial activity against M. tuberculosis H37Rv. The highest potency was also displayed by nitro-substituted compounds. The results of the present study are in a good agreement with our previous findings and confirm the positive influence of electron-withdrawing groups on the B-ring of chalcones on the antifungal and antimycobacterial activity of these compounds.
传染病，如结核病和侵袭性真菌病，是严重的健康问题。作为我们长期致力于寻找治疗这些疾病新药物的一部分，我们制备了一系列新的吡嗪类查耳酮类似物，其吡嗪环的5位带有异丙基。通过红外光谱和核磁共振光谱对化合物的结构进行了确证，并通过元素分析确认了其纯度。测试了八种真菌菌株对所研究化合物的敏感性。将结果与一些先前报道的丙基衍生物的活性进行了比较。唯一对所研究化合物敏感的菌株是须癣毛癣菌。结果发现，用支链异丙基取代直链丙基对体外抗须癣毛癣菌活性没有决定性的明确影响。硝基取代衍生物对须癣毛癣菌的体外活性与氟康唑相当。不幸的是，没有一种化合物表现出与特比萘芬相当的疗效，特比萘芬是治疗皮肤癣菌引起的真菌病最广泛使用的药物。对一些制备的化合物进行了抗结核分枝杆菌H37Rv的抗分枝杆菌活性测定。硝基取代的化合物也表现出最高的效力。本研究结果与我们之前的发现高度一致，并证实了查耳酮B环上的吸电子基团对这些化合物的抗真菌和抗分枝杆菌活性有积极影响。
