Biopolym. Cell. 2022; 38(1):48-57.
http://dx.doi.org/10.7124/bc.000A72
Bioorganic Chemistry
Synthesis and biological evaluation of O-acyloximes of 5-chloro-4-formyl- 1H-pyrrol-3-carboxylates as antimicrobial agents
1Grozav A. M., 1Chornous V. O., 1Diichuk I. V., 2Kemskyi S. V., 1Yakovychuk N. D., 3Fedoriv M. Z., 2Vovk M. V.
  1. Higher State Educational Establishment of Ukraine «Bukovinian State Medical University»
    2, Theatralna sq., Chernivtsi, Ukraine, 58002
  2. Institute of Organic Chemistry, NAS of Ukraine
    5, Murmanska Str., Kyiv, Ukraine, 02660
  3. Ivano-Frankivsk National Medical Universitу
    2, Halytska Str., Ivano-Frankivsk, Ukraine, 76018

Abstract

Aim. Elaboration of effective methods for the synthesis of the polysubstituted oximes with the O-acyloxime groups and investigation of their antibacterial and antifungal activity. Methods. organic synthesis, analytical and spectral methods, pharmaceutical screening. Results. A series of new O-acyloximes of 4-formylpyrroles has been synthesized, and the screening of their antibacterial and antifungal activity was performed. It was found that the synthesized compounds exhibit antimicrobial activity, and their minimum inhibitory concentration (MIC) is ranged between 7.81 and 125 μg/mL. A comparatively high antibacterial activity has been registered for some synthesized compounds against the gram-negative bacteria of the genus Proteus (MIC=7.8–62.5 μg/mL). Conclusions. The most active antibacterial O-acyloximes were identified among the array of the synthesized substances, and the MIC of the compound 10 consisting of an m-nitrobenzoilic fragment against the bacterial test strains Proteus aeruginosa ATCC 27853 and Proteus mirabilis ATCC 410 was 15.625 μg/mL. In the case of the latter strain, this value is close to the MIC value of the control drug. The MIC of the compound 9 against the bacterial strain Proteus mirabilis ATCC 410 was 7.81 μg/mL, which is greater than the corresponding control MIC.
Keywords: oximes of 4-formylpyrroles, acylation, О-acyloximes, antimicrobial activity
Full text: (PDF, in English)

References

[1] Rykaczewski KA, Wearing ER, Blackmun DE, Schindler CS. Reactivity of oximes for diverse methodologies and synthetic applications. Nat Synths. 2022; 1: 24-36.
[2] Vessally E, Saeidian H, Hosseinian A, Edjlali L, Bekhradni A. A review on synthetic applications of oxime esters. Curr Org Chem. 2016; 21 (3): 249-71.
[3] Koch P, Gehringer M, Laufer SA. Inhibitors of c-Jun N-terminal kinases - an update. J Med Chem. 2014; 58 (1): 72-95.
[4] Bachovchin DA, Wolfe MR, Masuda K, Brown SJ, Spicer TP, Fernandez-Vega V, Chase P, Hodder PS, Rosen H, Cravatt BF. Oxime esters as selective, covalent inhibitors of the serine hydrolase retinoblastoma-binding protein 9 (RBBP9). Bioorg Med Chem Lett. 2010; 29(7): 2254-8.
[5] Harini ST, Kumar HV, Rangaswamy J, Naik N. Synthesis, antioxidant and antimicrobial activity of novel vanillin derived piperidin-4-one oxime esters: Preponderant role of the phenyl ester substituents on the piperidin-4-one oxime core. Bioorg Med Chem Lett. 2012; 16 (22): 7588-92.
[6] Abdel-Hafez EMN, Abuo-Rahma GEAA, Abdel-Aziz M, Radwan MF, Farag HH. Design, synthesis and biological investigation of certain pyrazole-3-carboxylic acid derivatives as novel carriers for nitric oxide. Bioorg Med Chem. 2009; 17(11): 3829-37.
[7] Hu Q, Lin GS, Duan WG, Huang M, Lei F-H. Synthesis and biological activity of novel (Z)- and (E)-verbenone oxime esters. Molecules. 2017; 22(10): 1678-94.
[8] Gao Y, Song J, Shang S, Wang D, Li J. Synthesis and antibacterial activity of oxime esters from dihydrocumic acid. Bioresources. 2021; 7(3): 4150-60.
[9] Liu X-H, Zhi L, Song B, Xu H. Synthesis, characterization and antibacterial activity of new 5-aryl pyrazole oxime ester derivatives. Chem Res Chinese universities. 2008;24 (4): 454-8.
[10] Jeong HJ, Park Y-D, Park H-Y, Jeong IY, Jeonga T-S, Leea WS. Potent inhibitors of lipoprotein-associated phos-pholipase A2: Benzaldehyde O-heterocycle-4-carbonyloxime. Bioorg Med Chem Lett. 2006; 16(21): 5576-9.
[11] Sambath K, Zhao T, Wan Z, Zhang Y. Photouncaging of BODIPY oxime ester for histone deacetylases induced apoptosis in tumor cells. Chem Commun. 2019; 55(94): 14162-5.
[12] Shao N, Li J, Zhu H, Zhang S, Zou H. Functionalized N-containing heterocyclic scaffolds derived from N-substituted pyrroles via inter- and intramolecular annulations. Tetrahedron. 2018; 74 (42): 6088-94.
[13] Zhang Z, Li J, Zhang G, Ma N, Liu Q, Liu T. Iron-catalyzed intramolecular C(sp2)-Ncyclization of 1-(N-arylpyrrol-2-yl)ethanone O-acetyl oximes toward pyrrolo[1,2-a]quinoxaline derivatives. Org Chem. 2015; 80 (13): 6875-84.
[14] Abd El-Hameed RH, Sayed AI, Ali SM, Mosa MA, Khoder ZM, Fatahala SS. Synthesis of novel pyrroles and fused pyrroles as antifungal and antibacterial agents. J Enzyme Inhib Med Chem. 2021; 36 (1): 2183-98.
[15] Petri GL, Spanò V, Spatola R, Holl R, Raimondi MV, Barraja P, Montalbano A. Bioactive pyrrole-based com-pounds with target selectivity. Eur J Med Chem. 2020; 208: 112783.
[16] Bianco MCAD, Marinho DILF, Hoelz LVB, Bastos MM, Boechat N. Pyrroles as privileged scaffolds in the search for new potential HIV inhibitors. Pharmaceuticals. 2021; 14(9): 893.
[17] Klemm EJ, Wong VK, Dougan G. Emergence of dominant multidrug-resistant bacterial clades: Lessons from history and whole-genome sequencing. Proc Natl Acad Sci USA. 2018; 115(51): 12872-77.
[18] Hawkey PM, Warren RE, Livermore DM, McNulty CAM, Enoch DA, Otter JA, Wilson APR. Treatment of infections caused by multidrug-resistant gram-negative bacteria: report of the british society for antimicrobial chemo-therapy/healthcare infection society/british infection association joint working party. J Antimicrob Chemother. 2018; 73(Suppl_3): iii2-iii78.
[19] Sharma D, Sharma S, Sharma J. Potential strategies for the management of drug-resistant tuberculosis. J Glob Antimicrob Resist. 2020; 22: 210-4.
[20] Morel CM, Lindahl O, Harbarth S, de Kraker MEA, Edwards S, Hollis A. Industry incentives and antibiotic resistance: an introduction to the antibiotic susceptibility bonus. J Antibiot. 2020; 73(7): 421-8.
[21] Murray AK. The novel coronavirus COVID-19 outbreak: Global implications for antimicrobial resistance. Front Microbiol. 2020; 11: 1020.
[22] Kishida N, Nishiura H. Accelerating reductions in antimicrobial resistance: Evaluating the effectiveness of an intervention program implemented by an infectious disease consultant. Int J Infect Dis. 2020; 93: 175-81.
[23] Yakovychuk ND, Deyneka SY, Grozav AM, Humenna AV, Popovych VB, Djuiriak VS. Antifungal activity of 5-(2-nitrovinyl) imidazoles and their derivatives against the causative agents of vulvovaginal candidiasis. Reg Mech Biosyst. 2018; 9 (3), 369-73.
[24] Grozav AM, Fedoriv MZ, Chornous VO, Kemskyi SV, Vovk MV. Synthesis of 4-amino-5-chloro-2,6-dihydropyrrolo[3,4-d]pyridazin-1-ones. Vopr Khim Khim Tekhnol. 2020; 5: 11-7.
[25] Girlich D, Bonnin RA, Dortet L, Naas T. Genetics of acquired antibiotic resistance genes in Proteus spp. Front Microbiol. 2020; 11: 256.