1. Department of Chemistry, MPS International, Jaipur, Rajasthan, India 2. Department of Microbiology, Mahatma Gandhi University of Medical Sciences & Technology, Jaipur, Rajasthan, India 3. Department of Biotechnology, Invertis University, Bareilly, Uttar Pradesh, India
Микозы человека представляют серьезную угрозу для здоровья населения во всем мире. Для лечения этих заболеваний применяется ограниченное число противогрибковых препаратов. В данной работе исследовали противогрибковую активность ранее синтезированных спиро-1,4-дигидропиридинов (1,4-DHPs). Противогрибковую активность соединений спиро-1,4-DHPs проверяли в отношении Aspergillus flavus, A. fumigatus и Candida albicans с использованием метода дисковой диффузии и модифицированного микроразведения. Оценка противогрибковой активности против лекарственно-устойчивых вариантов грибов показала, что исследованные соединения обладают значительной противогрибковой активностью. Все шесть исследованных соединений спиро-1,4-DHPs проявляли более сильную противогрибковую активность в отношении A. flavus, A. fumigatus и C. albicans по сравнению с флуконазолом — стандартным противогрибковым препаратом, — по-видимому, за счёт ингибирования синтеза хитина в клеточной стенке. Три из шести соединений (4c, 4e и 4b) были наиболее эффективны в отношении A. fumigatus, A. flavus, C. albicans соответственно. Комбинация соединений показала, что синтезированные вещества обладают синергетическим, аддитивным действием по сравнению с применяемыми в настоящее время препаратами в качестве противогрибкового средства. Полученные результаты свидетельствуют о том, что синтезированные соединения являются потенциальными ингибиторами хитинсинтазы и обладают превосходной антимикотической активностью для лечения грибковых инфекций.
Шарма Г., Шарма Р., Саксена Р., Раджни Э., Пракаш Мамориа В. (2023) Фармакологическое значение новых спиро 1,4-дигидропиридинов против патогенных для человека грибов. Биомедицинская химия, 69(1), 55-61.
Шарма Г. и др. Фармакологическое значение новых спиро 1,4-дигидропиридинов против патогенных для человека грибов // Биомедицинская химия. - 2023. - Т. 69. -N 1. - С. 55-61.
Шарма Г. и др., "Фармакологическое значение новых спиро 1,4-дигидропиридинов против патогенных для человека грибов." Биомедицинская химия 69.1 (2023): 55-61.
Шарма, Г., Шарма, Р., Саксена, Р., Раджни, Э., Пракаш, Мамориа, В. (2023). Фармакологическое значение новых спиро 1,4-дигидропиридинов против патогенных для человека грибов. Биомедицинская химия, 69(1), 55-61.
Список литературы
Köhler J.R., Hube B., Puccia R., Casadevall A., Perfect J.R. (2017) Fungi that infect humans. Microbiology Spectrum, 5(3), 5-3. CrossRef Scholar google search
Limper A.H., Adenis A., Le T., Harrison T.S. (2017) Fungal infections in HIV/AIDS. Lancet Infectious Diseases, 17(11), e334-e343. CrossRef Scholar google search
Perlin D.S., Rautemaa-Richardson R., Alastruey-Izquierdo A. (2017) The global problem of antifungal resistance: Prevalence, mechanisms, and management. Lancet Infectious Diseases, 17(12), e383-e392. CrossRef Scholar google search
Sanglard D. (2016) Emerging threats in antifungal-resistant fungal pathogens. Front. Med., 3, 11. CrossRef Scholar google search
Holan Z., Pokorný V., Beran K., Gemperle A., Tuzar Z., Baldrián J. (1981) The glucan-chitin complex in Saccharomyces cerevisiae. Arch. Microbiol., 130(4), 312-318. CrossRef Scholar google search
Kreutzer D., Ritter C.A., Hilgeroth A. (2020) Novel nonsymmetrical 1,4-dihydropyridines as inhibitors of nonsymmetrical MRP-efflux pumps for anticancer therapy. Pharmaceuticals, 13(7), 146. CrossRef Scholar google search
Cataldi M., Bruno F. (2012) 1,4-Dihydropyridines: The multiple personalities of a blockbuster drug family. Transl. Med. UniSa, 4, 12-26. Scholar google search
Pajuste K., Rucins M., Domracheva I., Sobolev A., Pikun N., Plotniece M., Duburs G., Pajuste K., Plotniece A. (2020) Data for the cytotoxicity, self-assembling properties and synthesis of 4-pyridinium-1,4-dihydropyridines. Data Brief, 33, 1-16. CrossRef Scholar google search
Rucins M., Plotniece A., Bernotiene E., Tsai W.B., Sobolev A. (2020) Recent approaches to chiral 1,4-dihydropyridines and their fused analogues. Catalysts, 10(9), 1019. CrossRef Scholar google search
van der Vossen A.C., Cransberg K., de Winter B., Schreuder M.F., van Rooij-Kouwenhoven R.W., Vulto A.G., Hanff L.M. (2020) Use of amlodipine oral solution for the treatment of hypertension in children. Int. J. Clin. Pharmacy, 42(3), 848-852. CrossRef Scholar google search
Palatnick W., Jelic T. (2020) Calcium channel blocker and beta blocker overdose, and digoxin toxicity management. Emergency Medicine Practice, 22(9), 1-42. Scholar google search
Velena A., Zarkovic N., Gall Troselj K., Bisenieks E., Krauze A., Poikans J., Duburs G. (2016) 1,4-dihydropyridine derivatives: Dihydronicotinamide analogues – model compounds targeting oxidative stress. Oxid. Med. Cell. Longev., 2016, 1892412. CrossRef Scholar google search
Cui C.B., Kakeya H., Okada G., Onose R., Osada H. (1996) Novel mammalian cell cycle inhibitors, tryprostatins A, B and other diketopiperazines produced by Aspergillus fumigatus. I. Taxonomy, fermentation, isolation and biological properties. J. Antibiotics, 49(6), 527-533. Scholar google search
Tsuda M., Mugishima T., Komatsu K., Sone T., Tanaka M., Mikami Y., Shiro M., Hirai M., Ohizumii Y., Kobayashi J.I. (2003) Speradine A, a new pentacyclic oxindole alkaloid from a marine-derived fungus Aspergillus tamarii. Tetrahedron, 59(18), 3227-3230. CrossRef Scholar google search
Zhang X., Smith C.D. (1996) Microtubule effects of welwistatin, a cyanobacterial indolinone that circumvents multiple drug resistance. Mol. Pharmacol., 49(2), 288-294. Scholar google search
Efange S.M., Kamath A.P., Khare A.B., Kung M.P., Mach R.H., Parsons S.M. (1997) N-hydroxyalkyl derivatives of 3β-phenyltropane and 1-methylspiro [1H indoline-3,4‘-piperidine]: Vesamicol analogues with affinity for monoamine transporters. J. Med. Chem., 40(24), 3905-3914. CrossRef Scholar google search
Goehring R.R. (1995) Synthesis of a spirocyclic oxendole analogue as a putative replacement for Pr02-Pro3-Gly4-Phe5 in bradykinin antagonists. Organic Preparations Procedures International, 27(6), 691-694. CrossRef Scholar google search
Edmondson S., Danishefsky S.J., Sepp-Lorenzino L., Rosen N. (1999) Total synthesis of spirotryprostatin A, leading to the discovery of some biologically promising analogues. J. Am. Chem. Soc., 121(10), 2147-2155. CrossRef Scholar google search
Zhou L.M., Qu R.Y., Yang G.F. (2020) An overview of spirooxindole as a promising scaffold for novel drug discovery. Exp. Opin. Drug Discov., 15(5), 603-625. CrossRef Scholar google search
Vijesh A.M., Isloor A.M., Peethambar S.K., Shivananda K.N., Arulmoli T., Isloor N.A. (2011) Hantzsch reaction: Synthesis and characterization of some new 1,4-dihydropyridine derivatives as potent antimicrobial and antioxidant agents. Eur. J. Med. Chem., 46(11), 5591-5597. CrossRef Scholar google search
Mehta P., Verma P. (2013) Antimicrobial activity of some derivatives of 1,4-dihydropyridines. J. Chem., 2013, 1-4. CrossRef Scholar google search
Olejníková P., Švorc Ľ., Olšovská D., Panáková A., Vihonská Z., Kovaryová K., Marchalín Š. (2014) Antimicrobial activity of novel C2-substituted 1,4-dihydropyridine analogues. Scientia Pharmaceutica, 82(2), 221-232. CrossRef Scholar google search
Sepehri S., Sanchez H.P., Fassihi A. (2015) Hantzsch-type dihydropyridines and biginelli-type tetra-hydropyrimidines: A review of their chemotherapeutic activities. J. Pharm. Pharm. Sci., 18(1), 1-52. CrossRef Scholar google search
Tirzit G.D., Dubur G.Y. (1972) 1,4-dihydropyridines as inhibitors of free-radical reactions. Chem. Heterocycl. Comp., 8(1), 126-127. CrossRef Scholar google search
Khedkar S., Auti P.B. (2014) 1,4-Dihydropyridines: A class of pharmacologically important molecules. Mini Rev. Med. Chem., 14(3), 282-290. Scholar google search
Nix D.E., Swezey R.R., Hector R., Galgiani J.N. (2009) Pharmacokinetics of nikkomycin Z after single rising oral doses. Antimicrob. Agents Chemother., 53(6), 2517-2521. CrossRef Scholar google search
Sucher A.J., Chahine E.B., Balcer H.E. (2009) Echinocandins: The newest class of antifungals. Ann. Pharmacother., 43(10), 1647-1657. CrossRef Scholar google search
Cheung Y.Y., Hui M. (2017) Effects of echinocandins in combination with nikkomycin Z against invasive Candida albicans bloodstream isolates and the fks mutants. Antimicrob. Agents Chemother., 61(11), e00619-17. CrossRef Scholar google search
Sharma G., Sharma R., Sharma M., Dandia A., Bansal P. (2013) Synthesis and synergistic, additive inhibitory effects of novel spiro derivatives against ringworm infections. Russ. J. Bioorg. Chem., 39(3), 318-328. CrossRef Scholar google search
Gould J.C., Bowie J.H. (1952) The determination of bacterial sensitivity to antibiotics. Edinb. Med. J., 59(4), 178-199. Scholar google search
Provine H., Hadley S. (2000) Preliminary evaluation of a semisolid agar antifungal susceptibility test for yeasts and molds. J. Clin. Microbiol., 38(2), 537-541. CrossRef Scholar google search
Dandia A., Arya K. (2007) Synthesis and cytotoxic activity of trisubstituted-1,3,5-triazines. Bioorg. Med. Chem. Lett., 17(12), 3298-3304. Scholar google search
Dandia A., Sharma G., Singh R., Laxkar A. (2009) A new strategy for the synthesis of novel spiro[indoline-3,2'-thiazolo[5,4-e]pyrimido[1,2-a]pyrimidine] derivatives. Scholar google search
Kumar R.S., Idhayadhulla A., Nasser A.J.A., Selvin J. (2011) Synthesis and anticoagulant activity of a new series of 1,4-dihydropyridine derivatives. Eur. J. Med. Chem., 46(2), 804-810. CrossRef Scholar google search
Sirisha K., Achaiah G., Reddy V.M. (2010) Facile synthesis and antibacterial, antitubercular, and anticancer activities of novel 1,4-dihydropyridines. Archiv Der Pharmazie, 343(6), 342-352. CrossRef Scholar google search
Tempone A.G., Taniwaki N.N., Reimão J.Q. (2009) Antileishmanial activity and ultrastructural alterations of Leishmania chagasi (L.) treated with the calcium channel blocker nimodipine. Parasitol. Res., 105(2), 499-505. CrossRef Scholar google search
Baixench M.T., Aoun N., Desnos-Ollivier M., Garcia-Hermoso D., Bretagne S., Ramires S., Dannaoui E. (2007) Acquired resistance to echinocandins in Candida albicans: Case report and review. J. Antimicrob. Chemother., 59(6), 1076-1083. CrossRef Scholar google search
Niimi K., Monk B.C., Hirai A., Hatakenaka K., Umeyama T., Lamping E., Niimi M. (2010) Clinically significant micafungin resistance in Candida albicans involves modification of a glucan synthase catalytic subunit GSC1 (FKS1) allele followed by loss of heterozygosity. J. Antimicrob. Chemother., 65(5), 842-852. CrossRef Scholar google search
Munro C.A., Selvaggini S., de Bruijn I., Walker L., Lenardon M.D., Gerssen B., Gow N.A. (2007) The PKC, HOG and Ca2+ signaling pathways co-ordinately regulate chitin synthesis in Candida albicans. Mol. Microbiol., 63(5), 1399-1413. Scholar google search
Fortwendel J.R., Juvvadi P.R., Pinchai N., Perfect B.Z., Alspaugh J.A., Perfect J.R., Steinbach W.J. (2009) Differential effects of inhibiting chitin and 1,3-β-D-glucan synthesis in ras and calcineurin mutants of Aspergillus fumigatus. Antimicrob. Agents Chemother., 53(2), 476-482. CrossRef Scholar google search
Steinbach W.J., Reedy J.L., Cramer R.A., Perfect J.R., Heitman J. (2007) Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections. Nature Reviews Microbiology, 5(6), 418-430. CrossRef Scholar google search
