Synthesis, Molecular Docking and Biological Evaluation of Substituted Quinazolinones as Antibacterial Agents

Mahato, Arun; Shrivsatava, Birendra; Shanthi, Nithya

doi:10.7598/cst2015.995

Cited by 4 publications

(3 citation statements)

References 19 publications

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“…Вследствие такого взаимодействия происходит открытие активного сайта, в котором карбонильная группа и атом азота другой молекулы противомикробного агента ковалентно связываются с карбоксильной и аминогруппой лизина и аргинина. Происходит подавление работы фермента и, как следствие, блокирование биосинтеза клеточной стенки бактерии [37][38][39][40]. Анализ влияния различных заместителей в молекуле производных хиназолинона позволил выявить функциональные группы и структурные фрагменты, принимающие участие в образовании химической связи с остатками аминокислот фермента за счет чего, вероятно, реализуется фармакологический эффект веществ.…”

Section: оценка роста микроорганизмовunclassified

“…Описан механизм взаимодействия веществ с ДНК-гиразой, который также зависит от природы заместителей, определяющих полярность молекулы, ее способность образовывать различные химические связи с ферментом. Известно, что в данном случае гибель бактериальной клетки опосредована нарушением синтеза ДНК при ингибировании ДНК-гиразы, участвующей в раскручивании (отрицательной суперспирализации) молекулы нуклеиновой кислоты (НК), производным хиназолинона [37]. Установлено, что его влияние может быть объяснено образованием промежуточного комплекса «ДНК-топоизомераза-хиназолинон» за счет донорно-акцепторного взаимодействия атома кислорода карбонильной группы антимикробного агента и фосфатной группы ДНК, азота с гуанином и аспарагином НК, заместителей хиназолиноновой молекулы с ее неполярными группами.…”

Section: оценка роста микроорганизмовunclassified

“…Установлено, что его влияние может быть объяснено образованием промежуточного комплекса «ДНК-топоизомераза-хиназолинон» за счет донорно-акцепторного взаимодействия атома кислорода карбонильной группы антимикробного агента и фосфатной группы ДНК, азота с гуанином и аспарагином НК, заместителей хиназолиноновой молекулы с ее неполярными группами. Связывание с активным сайтом фермента происходит за счет водородных связей производного хиназолинона с аминокислотными остатками серина и аргинина [37].…”

Section: оценка роста микроорганизмовunclassified

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Antimicrobial Activity Study of New Quinazolin-4(3h)-Ones Against Staphylococcus Aureus and Streptococcus Pneumoniae

Самотруева

Озеров

Старикова

et al. 2021

Farm. farmakol. (Pâtigorsk)

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Quinazolin-4(3H)-one derivatives exhibiting a wide spectrum of a pharmacological activity, represent a promising class of substances used to obtain antibacterial agents, which is especially important in the context of the emergence of pathogenic microorganisms’ resistance to drugs used in medicine. It has been proved that compounds having a naphthyl radical in the molecule, as well as an amide group bound to the benzene ring as quinazolinone substituents, are characterized by a pronounced antimicrobial activity against Staphylococcus aureus and Streptococcus pneumoniae.The aim of the research is a primary microbiological screening of the in vitro antimicrobial activity of new quinazolin-4(3H)-one derivatives against Staphylococcus aureus and Streptococcus pneumoniae, as well as the assessment of the relationship between the pharmacological effect and the structural transformation of the substance molecule, lipophilicity and the possibility of forming resistance to them.Materials and methods. The experimental studies have been carried out using well-known nosocomial pathogens of infectious and inflammatory diseases Staphylococcus aureus and Streptococcus pneumoniae by a serial dilution method.Results. A compound containing a naphthyl radical in its structure, which contributes to an increase in the hydrophobicity of the substance and its solubility in the membrane of a bacterial cell, has a bacteriostatic effect against both Staphylococcus aureus and Streptococcus pneumoniae. A similar pharmacological effect is exhibited by a derivative with an amide group as a substituent of the quinazolinone nucleus linked to a phenyl radical, which probably contributes to an increase in the degree of binding to active sites of enzymes involved in the DNA replication, and protein synthesis. Obviously, the increased lipophilicity, which promotes better binding to the efflux protein, cannot serve as objective characteristics of the emergence possibility of the pathogen’s resistance to this substance.Conclusion. Among the synthesized compounds, the leading substances that exhibit an antimicrobial activity against Staphylococcus aureus and Streptococcus pneumonia, have been identified. The assessment of the chemical structure made it possible to substantiate their pharmacological action and draw conclusions about the possibility of developing resistance to it in microbial cells.

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Section: оценка роста микроорганизмовunclassified

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Antimicrobial Activity Study of New Quinazolin-4(3h)-Ones Against Staphylococcus Aureus and Streptococcus Pneumoniae

Самотруева

Озеров

Старикова

et al. 2021

Farm. farmakol. (Pâtigorsk)

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Biochemical Basis of the Antimicrobial Activity of Quinazolinone Derivatives in the Light of Insights into the Features of the Chemical Structure and Ways of Binding to Target Molecules. A Review

Samotrueva,

Starikova,

Bashkina

et al. 2023

Dokl Chem

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Biochemical Basis of the Antimicrobial Activity of Quinazolinone Derivatives in the Light of Insights Into the Features of the Chemical Structure and Ways of Binding to Target Molecules. A Review

Samotruyeva,

Starikova,

Bashkina

et al. 2023

Doklady Rossijskoj akademii nauk. Himiâ, nauki o materialah.

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The review characterizes the role of the main targets of antibacterial agents: “efflux pumps”; enzymes (DNA-hyruases as a subclass of topoisomerases, homoserine transacetylase, various classes of sorbitases, aromatics, lipoteichoyl synthase, polyketide synthase, pantothenate synthetase, acetyl-CoA carboxylase, sensory histidine kinase, kinase, cyclooxygenase, etc.); penicillin-binding protein; quorum signaling and adhesin systems in important biochemical processes of pathogen maintenance and virulence manifestation. The possibility of manifestation of antimicrobial effect by the substance upon its binding to the protein molecules responsible for pathogenicity of a microorganism was shown. The role of quinazolinone derivatives exhibiting high reactivity, stability in chemical processes and characterized by a wide spectrum of pharmacological activity including antimicrobial activity with respect to various gram-positive and gram-negative bacteria was determined. It has been shown that changes in the compound structure through the introduction of different substituents modify the degree of hydrophilicity and, as a result, determine a different degree of drug penetration through the cell membrane; the ability to form intermediate complex compounds stabilized by hydrogen bonds and van der Waals and stacking interactions with enzymatic targets as well as receptor-regulator proteins and signaling systems of pathogen cells. The results on prediction of the mechanism of action of the compounds synthesized by the authors of the article by methods of mathematical modeling are presented. The possibility of creating combined structures based on the quinazolinone core with various heterocyclic derivatives as a product with a pronounced antimicrobial activity is assessed. The considered regularities are of practical importance for the specialists in the field of medicinal chemistry, organic synthesis, biotechnology, clinical pharmacology, pharmaceutical chemistry and technology whose efforts are aimed at obtaining a new drug substance.

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Synthesis, Molecular Docking and Biological Evaluation of Substituted Quinazolinones as Antibacterial Agents

Cited by 4 publications

References 19 publications

Antimicrobial Activity Study of New Quinazolin-4(3h)-Ones Against Staphylococcus Aureus and Streptococcus Pneumoniae

Antimicrobial Activity Study of New Quinazolin-4(3h)-Ones Against Staphylococcus Aureus and Streptococcus Pneumoniae

Biochemical Basis of the Antimicrobial Activity of Quinazolinone Derivatives in the Light of Insights into the Features of the Chemical Structure and Ways of Binding to Target Molecules. A Review

Biochemical Basis of the Antimicrobial Activity of Quinazolinone Derivatives in the Light of Insights Into the Features of the Chemical Structure and Ways of Binding to Target Molecules. A Review

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