A Novel Synthetic Diterpene Reduces Mycobacterial Persistence and Biofilm Formation by Targeting (p)ppGpp Synthetases

Ткаченко, А. Г.; Kashevarova, Natalya M.; Sidorov, Roman Yu.; Nesterova, L. Yu.; Akhova, A. V.; Tsyganov, Ivan V.; Vaganov, Vladimir Yu.; Шипиловских, С. А.; Рубцов, А. Е.; Malkov, Andrei V.

doi:10.2139/ssrn.3696759

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“…Persister cell formation in Mycobacterium is highly dependent on the alarmone (p)ppGpp and its essential Rel protein. The analogue 4-(4,7-di-methyl-1,2,3,4-tetrahydro-naphthalene-1yl)pentanoic acid (DMNP) (4) (Figure 4) was found to inhibit RelMsm activity of (p)ppGppsynthesis in a concentration-dependent manner [154]. Furthermore, docking studies suggested the interaction of DMNP with RelZ and RelMsm proteins and high affinity with their GTP binding sites, consequently impeding their (p)ppGpp-synthesizing activity [155].…”

Section: Inhibition Of Persister Cell Formation By a Synthetic Diterpenementioning

confidence: 99%

Development of Antibiofilm Therapeutics Strategies to Overcome Antimicrobial Drug Resistance

et al. 2022

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A biofilm is a community of stable microorganisms encapsulated in an extracellular matrix produced by themselves. Many types of microorganisms that are found on living hosts or in the environment can form biofilms. These include pathogenic bacteria that can serve as a reservoir for persistent infections, and are culpable for leading to a broad spectrum of chronic illnesses and emergence of antibiotic resistance making them difficult to be treated. The absence of biofilm-targeting antibiotics in the drug discovery pipeline indicates an unmet opportunity for designing new biofilm inhibitors as antimicrobial agents using various strategies and targeting distinct stages of biofilm formation. The strategies available to control biofilm formation include targeting the enzymes and proteins specific to the microorganism and those involved in the adhesion pathways leading to formation of resistant biofilms. This review primarily focuses on the recent strategies and advances responsible for identifying a myriad of antibiofilm agents and their mechanism of biofilm inhibition, including extracellular polymeric substance synthesis inhibitors, adhesion inhibitors, quorum sensing inhibitors, efflux pump inhibitors, and cyclic diguanylate inhibitors. Furthermore, we present the structure–activity relationships (SAR) of these agents, including recently discovered biofilm inhibitors, nature-derived bioactive scaffolds, synthetic small molecules, antimicrobial peptides, bioactive compounds isolated from fungi, non-proteinogenic amino acids and antibiotics. We hope to fuel interest and focus research efforts on the development of agents targeting the uniquely complex, physical and chemical heterogeneous biofilms through a multipronged approach and combinatorial therapeutics for a more effective control and management of biofilms across diseases.

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Section: Inhibition Of Persister Cell Formation By a Synthetic Diterpenementioning

confidence: 99%

Development of Antibiofilm Therapeutics Strategies to Overcome Antimicrobial Drug Resistance

et al. 2022

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“…The compound and its analogues showed promising activity against clinical isolates of Mycobacterium tuberculosis, including a multidrugresistant strain. 67…”

Section: Account Synlettmentioning

confidence: 99%

Developing a Methodology for Catalytic Asymmetric Crotylation of Aldehydes

Рубцов

Malkov

2021

Synlett

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Asymmetric crotylation has firmly earned a place among the set of valuable synthetic tools for stereoselective construction of carbon skeletons. For a long time the field was heavily dominated by reagents bearing stoichiometric chiral auxiliaries, but now catalytic methods are gradually taking center stage, and the area continues to develop rapidly. This account focuses primarily on preformed organometallic reagents based on silicon and, to some extent, boron. It narrates our endeavors to design new and efficient chiral Lewis base catalysts for the asymmetric addition of crotyl(trichloro)silanes to aldehydes. It also covers the development of a novel protocol for kinetic resolution of racemic secondary allylboronates to give enantio- and diastereomerically enriched linear homoallylic alcohols. As a separate topic, cross-crotylation of aldehydes by using enantiopure branched homoallylic alcohols as a source of crotyl groups is discussed. Finally, the synthetic credentials of the developed methodology are illustrated by total syntheses of marine natural products, in which crotylation plays a key role in setting up stereogenic centers.1 Introduction2 Pyridine N-Oxides as Lewis Base Catalysts3 Bipyridine N,N′-Dioxides as Lewis Base Catalysts4 Chiral Allylating Reagents5 Synthetic Applications6 Concluding Remarks

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A Novel Synthetic Diterpene Reduces Mycobacterial Persistence and Biofilm Formation by Targeting (p)ppGpp Synthetases

Cited by 2 publications

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Development of Antibiofilm Therapeutics Strategies to Overcome Antimicrobial Drug Resistance

Development of Antibiofilm Therapeutics Strategies to Overcome Antimicrobial Drug Resistance

Developing a Methodology for Catalytic Asymmetric Crotylation of Aldehydes

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