Synthesis and antifungal activity of new hybrids thiazolo[4,5-d]pyrimidines with (1H-1,2,4)triazole

Blokhina, Svetlana V.; Sharapova, Angelica; Ol’khovich, Marina V.; Doroshenko, Irina A.; Levshin, I. B.; Perlovich, German L.

doi:10.1016/j.bmcl.2021.127944

Cited by 29 publications

(19 citation statements)

References 25 publications

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“…The methodology of synthesis of three novel antimycotic compounds as objects of the present investigation were synthesized by the methodology described in detail earlier [ 7 ]. In brief, a series of hybrid derivatives containing a piperazine linker between the triazole and pyrimidino[4,5-d]thiazol heterocycles was obtained by alkylation of the piperidine fragment imino group with haloalkyl.…”

Section: Methodsmentioning

confidence: 99%

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Experimental Examination of Solubility and Lipophilicity as Pharmaceutically Relevant Points of Novel Bioactive Hybrid Compounds

et al. 2022

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The important physicochemical properties of three novel bioactive hybrid compounds with different groups (-CH3, -F and -Cl) were studied, including kinetic and thermodynamic solubility in pharmaceutically relevant solvents (buffer solutions and 1-octanol) as well as partition coefficient in system 1-octanol/buffer pH 7.4. The aqueous solubility of these chemicals is poor and ranged from 0.67 × 10−4 to 1.98 × 10−3 mol·L−1. The compounds studied are more soluble in the buffer pH 2.0, simulating the gastrointestinal tract environment (by an order of magnitude) than in the buffer pH 7.4 modelling plasma of blood. The solubility in 1-octanol is significantly higher; that is because of the specific interactions of the compounds with the solvent. The prediction solubility behaviour of the hybrid compounds using Hansen’s three-parameter approach showed acceptable results. The experimental solubility of potential drugs was successfully correlated by means of two commonly known equations: modified Apelblat and van’t Hoff. The temperature dependencies of partition coefficients of new hybrids in the model system 1-octanol/buffer pH 7.4 as a surrogate lipophilicity were measured by the shake flask method. It was found that compounds demonstrated a lipophilic nature and have optimal values of partition coefficients for oral absorption. Bioactive assay manifested that prepared compounds showed antifungal activities equal to or greater than fluconazole. In addition, the thermodynamic aspects of dissolution and partition processes have been examined. Bioactive assay manifested that prepared compounds showed antifungal activities equal to or greater than the reference drug.

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Section: Methodsmentioning

confidence: 99%

“…The objects of this study are new hybrid compounds containing a combination of fluconazole and a thiazolo[4,5-d]pyrimidine fragment linked by a piperazine spacer [ 7 ]. The synthetic pathway of target hybrids is presented in Figure 1 .…”

Section: Introductionmentioning

confidence: 99%

Experimental Examination of Solubility and Lipophilicity as Pharmaceutically Relevant Points of Novel Bioactive Hybrid Compounds

et al. 2022

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“…Blokhina et al [ 29 ] investigated the fungicidal activity of thiazolo[4,5- d ] pyrimidine hybrids with (1 H- 1,2,4) triazole. All derivatives include the methyl-(2a), fluoro-(2b), and chloro-(2c) substituents at the para position.…”

Section: 124 Triazole Scaffold For the Development Of Antifungal Agentsmentioning

confidence: 99%

Novel 1, 2, 4-Triazoles as Antifungal Agents

Kazeminejad

Marzi

Shiroudi

et al. 2022

BioMed Research International

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The development of innovative antifungal agents is essential. Some fungicidal agents are no longer effective due to resistance development, various side effects, and high toxicity. Therefore, the synthesis and development of some new antifungal agents are necessary. 1,2,4-Triazole is one of the most essential pharmacophore systems between five-membered heterocycles. The structure-activity relationship (SAR) of this nitrogen-containing heterocyclic compound showed potential antifungal activity. The 1,2,4-triazole core is present as the nucleus in a variety of antifungal drug categories. The most potent and broad activity of triazoles have confirmed them as pharmacologically significant moieties. The goal of this review is to highlight recent developments in the synthesis and SAR study of 1,2,4-triazole as a potential fungicidal compound. In this study, we provide the results of a biological activity evaluation using various structures and figures. Literature investigation showed that 1, 2, 4-triazole derivatives reveal the extensive span of antifungal activity. This review will assist researchers in the development of new potential antifungal drug candidates with high effectiveness and selectivity.

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“…The extended use of fungicides with similar modes of action (MoA) exerts significant selection pressure on pathogen populations and increases the risk of antifungal resistance development. − It has been estimated that only four fungicide types constitute approximately 76% of the worldwide fungicide market, namely, dithiocarbamates, demethylation inhibitors (DMIs), strobilurins, and succinate dehydrogenase inhibitors (SDHIs). The development of cross-resistance in pathogenic strains of fungi due to the use of similar compounds both in medicine and in agriculture is also a matter of concern. − Thus, the discovery of new classes of fungicides with novel MoA is very important for both medicine and crop protection. − …”

Section: Introductionmentioning

confidence: 99%

4-Nitropyrazolin-5-ones as Readily Available Fungicides of the Novel Structural Type for Crop Protection: Atom-Efficient Scalable Synthesis and Key Structural Features Responsible for Activity

Budnikov

Lopat’eva

Krylov

et al. 2022

J. Agric. Food Chem.

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The development of new types of fungicides for agriculture and medicine is highly desirable due to the uprising fungal resistance against commonly used compounds. Herein, 4-substituted-4-nitropyrazolin-5-ones (nitropyrazolones) were proposed as highly active fungicides of the novel structural type. The first scalable and practical method for the nitropyrazolone synthesis was proposed, which is atom-efficient, is applicable for the multigram scale synthesis, and allows for production of a wide variety of nitropyrazolones with high yields and purity. The synthesized compounds demonstrated high fungicidal activity against the broad spectrum of phytopathogenic fungi (Venturia inaequalis, Rhizoctonia solani, Fusarium oxysporum, Fusarium moniliforme, Bipolaris sorokiniana, and Sclerotinia sclerotiorum). Their mycelium growth inhibiting activity was comparable or superior to that of kresoximmethyl. In vitro activity against Staphyloccocus aureus, Candida albicans, and Aspergillus niger revealed that nitropyrazolones are promising candidates against human pathogens. The key factors for the manifestation of high fungicidal activity were established to be an aromatic substituent on the N1 atom and small substituents, such as methyl, at the C3 and C4 positions of the pyrazolone ring.

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Synthesis and antifungal activity of new hybrids thiazolo[4,5-d]pyrimidines with (1H-1,2,4)triazole

Cited by 29 publications

References 25 publications

Experimental Examination of Solubility and Lipophilicity as Pharmaceutically Relevant Points of Novel Bioactive Hybrid Compounds

Experimental Examination of Solubility and Lipophilicity as Pharmaceutically Relevant Points of Novel Bioactive Hybrid Compounds

Novel 1, 2, 4-Triazoles as Antifungal Agents

4-Nitropyrazolin-5-ones as Readily Available Fungicides of the Novel Structural Type for Crop Protection: Atom-Efficient Scalable Synthesis and Key Structural Features Responsible for Activity

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