Aminonitrones as highly reactive bifunctional synthons. An expedient one-pot route to 5-amino-1,2,4-triazoles and 5-amino-1,2,4-oxadiazoles – potential antimicrobials targeting multi-drug resistant bacteria

Il’in, Mikhail V.; Sysoeva, Alexandra A.; Bolotin, Dmitrii S.; Novikov, Alexander S.; Suslonov, Vitalii V.; Rogacheva, Elizaveta; Краева, Л. А.; Kukushkin, Vadim Yu.

doi:10.1039/c9nj04529e

Cited by 10 publications

(5 citation statements)

References 86 publications

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“…Considering the importance of chemical stability, all oxazolium derivatives were also excluded because the high electrophilicity of these compounds rendered them unstable to reactions with common nucleophiles, including H 2 O. [42][43][44][45] Overall, fourteen structural types of iodoazoliums were evaluated in this study while keeping within these limitations (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

Predicting the catalytic activity of azolium-based halogen bond donors: an experimentally-verified theoretical study

et al. 2021

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Section: Resultsmentioning

confidence: 99%

Predicting the catalytic activity of azolium-based halogen bond donors: an experimentally-verified theoretical study

et al. 2021

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“…Along with these, other routes such as intramolecular cyclization of ester clubbed with amidoxime (Route E) have been reported by Raval et al [ 59 ] with high atom economy. Another excellent approach involving use of aminonitrone, hydroxylamine and isocyanide at rt to yield 1,2,4-oxadiazole (Route F) has been also attempted for the synthesis of anti-infective 1,2,4-oxadiazoles [ 60 ]. The present review article has been organized with the focus on the synthetic strategies using all these routes A–F.…”

Section: Synthetic Account Of 124-oxadizoles With Anti-infective Activitymentioning

confidence: 99%

“…Kukushkin and coworkers reported 5-amino-1,2,4-oxadiazoles ( 93 ) with higher anti-bacterial activity against multidrug-resistant strains such as Staphylococcus aureus and Klebsiella pneumonia (Scheme 15 ) [ 60 ]. These were prepared from different synthetic strategies involving the use of aminonitrone ( 90 ), hydroxylamine ( 91 ) and isocyanide ( 92 ) at rt in 29–86% yields.…”

Section: Synthetic Account Of 124-oxadizoles With Anti-infective Activitymentioning

confidence: 99%

A review on synthetic account of 1,2,4-oxadiazoles as anti-infective agents

et al. 2022

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Graphical abstract Most of the currently marketed drugs consist of heterocyclic scaffolds containing nitrogen and or oxygen as heteroatoms in their structures. Several research groups have synthesized diversely substituted 1,2,4-oxadiazoles as anti-infective agents having anti-bacterial, anti-viral, anti-leishmanial, etc. activities. For the first time, the present review article will provide the coverage of synthetic account of 1,2,4-oxadiazoles as anti-infective agents along with their potential for SAR, activity potential, promising target for mode of action. The efforts have been made to provide the chemical intuitions to the reader to design new chemical entity with potential of anti-infective activity. This review will mark the impact as the valuable, comprehensive and pioneered work along with the library of synthetic strategies for the organic and medicinal chemists for further refinement of 1,2,4-oxadiazole as anti-infective agents.

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“…Interestingly, phidianidine A was identified as an antifoulant agent which is a chemical defense of slow-moving marine organisms to deter predators, other colonizers, or competitors [21]. In the past two decades, a great number of 1,2,4oxadiazole derivates were synthesized and studied for their pharmacological properties, which exhibit numerous bioactivities, including anti-cancer [22,23], anti-inflammatory [24], anti-bacterial [25], anti-viral [26], anti-malarial [27], anti-diabetic [28], and anti-Alzheimer activities [29]. Zibotentan represents an example of an oxadiazole that reached a clinical phase III trial for the treatment of hormone-resistant prostate carcinoma [30].…”

Section: Introductionmentioning

confidence: 99%

Modes of Action of a Novel c-MYC Inhibiting 1,2,4-Oxadiazole Derivative in Leukemia and Breast Cancer Cells

et al. 2023

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The c-MYC oncogene regulates multiple cellular activities and is a potent driver of many highly aggressive human cancers, such as leukemia and triple-negative breast cancer. The oxadiazole class of compounds has gained increasing interest for its anticancer activities. The aim of this study was to investigate the molecular modes of action of a 1,2,4-oxadiazole derivative (ZINC15675948) as a c-MYC inhibitor. ZINC15675948 displayed profound cytotoxicity at the nanomolar range in CCRF-CEM leukemia and MDA-MB-231-pcDNA3 breast cancer cells. Multidrug-resistant sublines thereof (i.e., CEM/ADR5000 and MDA-MB-231-BCRP) were moderately cross-resistant to this compound (<10-fold). Molecular docking and microscale thermophoresis revealed a strong binding of ZINC15675948 to c-MYC by interacting close to the c-MYC/MAX interface. A c-MYC reporter assay demonstrated that ZINC15675948 inhibited c-MYC activity. Western blotting and qRT-PCR showed that c-MYC expression was downregulated by ZINC15675948. Applying microarray hybridization and signaling pathway analyses, ZINC15675948 affected signaling routes downstream of c-MYC in both leukemia and breast cancer cells as demonstrated by the induction of DNA damage using single cell gel electrophoresis (alkaline comet assay) and induction of apoptosis using flow cytometry. ZINC15675948 also caused G2/M phase and S phase arrest in CCRF-CEM cells and MDA-MB-231-pcDNA3 cells, respectively, accompanied by the downregulation of CDK1 and p-CDK2 expression using western blotting. Autophagy induction was observed in CCRF-CEM cells but not MDA-MB-231-pcDNA3 cells. Furthermore, microarray-based mRNA expression profiling indicated that ZINC15675948 may target c-MYC-regulated ubiquitination, since the novel ubiquitin ligase (ELL2) was upregulated in the absence of c-MYC expression. We propose that ZINC15675948 is a promising natural product-derived compound targeting c-MYC in c-MYC-driven cancers through DNA damage, cell cycle arrest, and apoptosis.

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Aminonitrones as highly reactive bifunctional synthons. An expedient one-pot route to 5-amino-1,2,4-triazoles and 5-amino-1,2,4-oxadiazoles – potential antimicrobials targeting multi-drug resistant bacteria

Abstract: A four-component one-pot reaction proceeds very rapidly under mild conditions and gives the heterocyclic systems in good yields.

Cited by 10 publications

References 86 publications

Predicting the catalytic activity of azolium-based halogen bond donors: an experimentally-verified theoretical study

Predicting the catalytic activity of azolium-based halogen bond donors: an experimentally-verified theoretical study

A review on synthetic account of 1,2,4-oxadiazoles as anti-infective agents

Modes of Action of a Novel c-MYC Inhibiting 1,2,4-Oxadiazole Derivative in Leukemia and Breast Cancer Cells

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