人类霉菌病已成为全球健康的威胁。不幸的是,使用的抗真菌药物数量有限。在本研究中,研究了较早合成的螺-1,4-二氢吡啶(1,4-DHP)的抗真菌活性。筛选了螺-1,4-DHPs化合物对黄曲霉的抗真菌活性,A.烟,和白色念珠菌的椎间盘扩散和改良微稀释法。在测试的六种螺-1,4-DHP化合物中,所有化合物均显示出更强的抗真菌活性,可能是通过抑制细胞壁中几丁质对黄曲霉的合成,A.烟,和白色念珠菌与氟康唑相比,一种标准的抗真菌药物.化合物的组合表明,合成的化合物具有协同作用,与目前用作抗真菌剂的药物相比,具有附加作用。这些结果表明,这些设计的化合物是潜在的几丁质合酶抑制剂,并具有出色的抗真菌活性用于治疗真菌感染。
Mikozychelovekapredstavliaiutser\'eznuiuugrozudliazdorov\'ianaseleniiavovsemmire.Dlialecheniiaétikhzabolevaniaéprimeniaetsiaogranichennoechisloprovogribkykhpreparatov.Vdannoàraboteissledovaliprotivogribkovuuaktivnost\'Raneesinterovannykhspiro-1,4-digitropiridinov(1,4-DHP)。Provigogribkovuuaktivnost\'soedinenianispiro-1,4-DHPproverialivotnoshenii黄曲霉,A.Fumigatusi白色念珠菌sispol\'zovaniemmetodadiskovovodiffuziiimodifitsirovannogomikrorazvedeniia.Otsenkaprotivogribkovoàaktivnostiprotivlekarstvenno-ustochivykhvariantovgribovpokazala,伊兹雷多凡尼苏伊迪尼尼亚奥布拉德特·纳希特尔\'不protivogribkovoaktivnost\'iu.Vseshest\'issledovannykhsoedinenikhspiro-1,4-DHPproiavlialiboleesil\'nuiuprotivogribkovuiuaktivnost\'votnosheniiA.flavus,A.fumigatusiC.albicansposravneniusflukonazolom-standartnymprotivogribkovympreparatatom,-po-vidimomu,zaschetingibirovaniiasintezakhitinavkletochno而stenke.Triizsheestisoedinenive(4c,4ei4b)bylinaiboleeéffektivnyvotnosheniiA.fumigatus,A.黄花,C.白色念珠菌。Kombinatsiiasoedineniopokazala,chtosintezirovannyeveshchestvaobladaiutsinergeticheskim,additivnymdestviemposravneniusprimeniaemymivnastoiashcheevremiapreparatamivkachestveprovigribkovogosredstva.Poluchennyerezul\'tatysvidettel\'stvuiutotom,对sintezirovannyesoedineniiaiavliaiutsiapotentsial\'nymiingibitoramikhitinintazyiobladaiutprevoskhodnodnot\'iudlialecheniiagribkovykhinfeektsit.
Human mycoses have become a threat to health world-wide. Unfortunately there are only a limited number of
antimycotic drugs in use. In the present study, antifungal activity of earlier synthesized spiro-1,4-dihydropyridines (1,4-DHPs) was investigated. The antifungal activity of spiro-1,4-DHPs compounds were screened against Aspergillus flavus, A. fumigatus, and Candida albicans by using Disc Diffusion and Modified Microdilution method. Among six spiro-1,4-DHPs compounds tested all of them showed stronger antifungal activity possibly through inhibiting the synthesis of chitin in cell wall against A. flavus, A. fumigatus, and C. albicans as compared to fluconazole, a standard antifungal drug. The combination of compounds showed that the synthesized compounds had synergistic, additive effects as compared to currently used drugs as an antifungal agent. These results indicated that these designed compounds were potential chitin synthase inhibitors and had excellent
antimycotic activity for the treatment of fungal infections.
Mikozy cheloveka predstavliaiut ser\'eznuiu ugrozu dlia zdorov\'ia naseleniia vo vsem mire. Dlia lecheniia étikh zabolevaniĭ primeniaetsia ogranichennoe chislo protivogribkovykh preparatov. V dannoĭ rabote issledovali protivogribkovuiu aktivnost\' ranee sintezirovannykh spiro-1,4-digidropiridinov (1,4-DHPs). Protivogribkovuiu aktivnost\' soedineniĭ spiro-1,4-DHPs proveriali v otnoshenii Aspergillus flavus, A. fumigatus i Candida albicans s ispol\'zovaniem metoda diskovoĭ diffuzii i modifitsirovannogo mikrorazvedeniia. Otsenka protivogribkovoĭ aktivnosti protiv lekarstvenno-ustoĭchivykh variantov gribov pokazala, chto issledovannye soedineniia obladaiut znachitel\'noĭ protivogribkovoĭ aktivnost\'iu. Vse shest\' issledovannykh soedineniĭ spiro-1,4-DHPs proiavliali bolee sil\'nuiu protivogribkovuiu aktivnost\' v otnoshenii A. flavus, A. fumigatus i C. albicans po sravneniiu s flukonazolom — standartnym protivogribkovym preparatom, — po-vidimomu, za schet ingibirovaniia sinteza khitina v kletochnoĭ stenke. Tri iz shesti soedineniĭ (4c, 4e i 4b) byli naibolee éffektivny v otnoshenii A. fumigatus, A. flavus, C. albicans sootvetstvenno. Kombinatsiia soedineniĭ pokazala, chto sintezirovannye veshchestva obladaiut sinergeticheskim, additivnym deĭstviem po sravneniiu s primeniaemymi v nastoiashchee vremia preparatami v kachestve protivogribkovogo sredstva. Poluchennye rezul\'taty svidetel\'stvuiut o tom, chto sintezirovannye soedineniia iavliaiutsia potentsial\'nymi ingibitorami khitinsintazy i obladaiut prevoskhodnoĭ antimikoticheskoĭ aktivnost\'iu dlia lecheniia gribkovykh infektsiĭ.