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1.
Pathogens ; 10(7)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34358036

RESUMO

Staphylococcus aureus infections represent a great concern due to their versatility and involvement in different types of diseases. The shortage of available clinical options, especially to treat multiresistant strains, makes the discovery of new effective compounds essential. Here we describe the activity of the previously described cell division inhibitor C109 against methicillin-sensitive and -resistant S. aureus strains. Antibiofilm activity was assessed using microtiter plates, confocal microscopy, and in an in vitro biofilm wound model. The ability of C109 to block FtsZ GTPase activity and polymerization was tested in vitro. Altogether, the results show that the FtsZ inhibitor C109 has activity against a wide range of S. aureus strains and support its use as an antistaphylococcal compound.

2.
J Chem Inf Model ; 61(8): 3804-3813, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34286575

RESUMO

Yellow fever (YF) is an acute viral hemorrhagic disease transmitted by infected mosquitoes. Large epidemics of YF occur when the virus is introduced into heavily populated areas with high mosquito density and low vaccination coverage. The lack of a specific small molecule drug treatment against YF as well as for homologous infections, such as zika and dengue, highlights the importance of these flaviviruses as a public health concern. With the advancement in computer hardware and bioactivity data availability, new tools based on machine learning methods have been introduced into drug discovery, as a means to utilize the growing high throughput screening (HTS) data generated to reduce costs and increase the speed of drug development. The use of predictive machine learning models using previously published data from HTS campaigns or data available in public databases, can enable the selection of compounds with desirable bioactivity and absorption, distribution, metabolism, and excretion profiles. In this study, we have collated cell-based assay data for yellow fever virus from the literature and public databases. The data were used to build predictive models with several machine learning methods that could prioritize compounds for in vitro testing. Five molecules were prioritized and tested in vitro from which we have identified a new pyrazolesulfonamide derivative with EC50 3.2 µM and CC50 24 µM, which represents a new scaffold suitable for hit-to-lead optimization that can expand the available drug discovery candidates for YF.


Assuntos
Febre Amarela , Infecção por Zika virus , Zika virus , Animais , Antivirais/farmacologia , Descoberta de Drogas , Aprendizado de Máquina , Vírus da Febre Amarela
3.
ACS Med Chem Lett ; 12(5): 774-781, 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34055225

RESUMO

Opportunistic infections from pathogenic fungi present a major challenge to healthcare because of a very limited arsenal of antifungal drugs, an increasing population of immunosuppressed patients, and increased prevalence of resistant clinical strains due to overuse of the few available antifungals. Cryptococcal meningitis is a life-threatening opportunistic fungal infection caused by one of two species in the Cryptococcus genus, Cryptococcus neoformans and Cryptococcus gattii. Eighty percent of cryptococcosis diseases are caused by C. neoformans that is endemic in the environment. The standard of care is limited to old antifungals, and under a high standard of care, mortality remains between 10 and 30%. We have identified a series of 5-nitro-6-thiocyanatopyrimidine antifungal drug candidates using in vitro and computational machine learning approaches. These compounds can inhibit C. neoformans growth at submicromolar levels, are effective against fluconazole-resistant C. neoformans and a clinical strain of C. gattii, and are not antagonistic with currently approved antifungals.

4.
Viruses ; 13(3)2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809292

RESUMO

Human cytomegalovirus (HCMV), a member of the betaherpesvirinae, can cause life-threatening diseases. HCMV is globally widespread, with a seroprevalence in adults varying from 50 to 100%. HCMV infection is rarely of significant consequence in immunocompetent individuals. However, although immune control is efficient, it cannot achieve the clearance of the virus. HCMV persists lifelong in the infected host and reactivates in certain circumstances. In neonates and in immunocompromised adults, HCMV is a serious pathogen that can cause fatal organ damage. Different antiviral compounds alone or in combination have been used for the treatment of HCMV diseases. In clinical use, mutations in the viral DNA polymerase or the terminase confer resistance to ganciclovir, foscarnet, cidofovir, and letermovir. There is an urgent need to find new well-tolerated compounds supporting different modes of action. The list of novel small molecules that might have anti-HCMV activity has grown in recent years. In this short review, a selection of compounds in clinical trials and novel inhibitors targeting host-cell factors or viral proteins is presented, and their modes of action, described.


Assuntos
Antivirais/farmacologia , Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/efeitos dos fármacos , Proteínas Virais/antagonistas & inibidores , Descoberta de Drogas , Humanos , Hospedeiro Imunocomprometido , Replicação Viral/efeitos dos fármacos
5.
Med Res Rev ; 41(4): 2350-2387, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33645845

RESUMO

The Mycobacterium abscessus complex is a group of emerging pathogens that are difficult to treat. There are no effective drugs for successful M. abscessus pulmonary infection therapy, and existing drug regimens recommended by the British or the American Thoracic Societies are associated with poor clinical outcomes. Therefore, novel antibacterial drugs are urgently needed to contain this global threat. The current anti-M. abscessus small-molecule drug development process can be enhanced by two parallel strategies-discovery of compounds from new chemical classes and commercial drug repurposing. This review focuses on recent advances in the finding of novel small-molecule agents, and more particularly focuses on the activity, mode of action and structure-activity relationship of promising inhibitors from five different chemical classes-benzimidazoles, indole-2-carboxamides, benzothiazoles, 4-piperidinoles, and oxazolidionones. We further discuss some other interesting small molecules, such as thiacetazone derivatives and benzoboroxoles, that are in the early stages of drug development, and summarize current knowledge about the efficacy of repurposable drugs, such as rifabutin, tedizolid, bedaquiline, and others. We finally review targets of therapeutic interest in M. abscessus that may be worthy of future drug and adjunct therapeutic development.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Preparações Farmacêuticas , Antibacterianos/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Rifabutina
6.
Sci Rep ; 11(1): 5110, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658528

RESUMO

Although quantum communication systems are being deployed on a global scale, their realistic security certification is not yet available. Here we present a security evaluation and improvement protocol for complete quantum communication systems. The protocol subdivides a system by defining seven system implementation sub-layers based on a hierarchical order of information flow; then it categorises the known system implementation imperfections by hardness of protection and practical risk. Next, an initial analysis report lists all potential loopholes in its quantum-optical part. It is followed by interactions with the system manufacturer, testing and patching most loopholes, and re-assessing their status. Our protocol has been applied on multiple commercial quantum key distribution systems to improve their security. A detailed description of our methodology is presented with the example of a subcarrier-wave system. Our protocol is a step towards future security evaluation and security certification standards.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33495228

RESUMO

Herpesviruses are widespread and can cause serious illness. Many currently available antiviral drugs have limited effects, result in rapid development of resistance, and often exhibit dose-dependent toxicity. Especially for human cytomegalovirus (HCMV), new well-tolerated compounds with novel mechanisms of action are urgently needed. In this study, we characterized the antiviral activity of two new diazadispiroalkane derivatives, 11826091 and 11826236. These two small molecules exhibited strong activity against low-passage-number HCMV. Pretreatment of cell-free virus with these compounds greatly reduced infection. Time-of-addition assays where 11826091 or 11826236 was added to cells before infection, before and during infection, or during or after infection demonstrated an inhibitory effect on early steps of infection. Interestingly, 11826236 had an effect by addition to cells after infection. Results from entry assays showed the major effect to be on attachment. Only 11826236 had a minimal effect on penetration comparable to heparin. Further, no effect on virus infection was found for cell lines with a defect in heparan sulfate expression or lacking all surface glycosaminoglycans, indicating that these small molecules bind to heparan sulfate on the cell surface. To test this further, we extended our analyses to pseudorabies virus (PrV), a member of the Alphaherpesvirinae, which is known to use cell surface heparan sulfate for initial attachment via nonessential glycoprotein C (gC). While infection with PrV wild type was strongly impaired by 11826091 or 11826236, as with heparin, a mutant lacking gC was unaffected by either treatment, demonstrating that primary attachment to heparan sulfate via gC is targeted by these small molecules.


Assuntos
Herpesvirus Suídeo 1 , Internalização do Vírus , Alcanos , Animais , Antivirais , Glicosaminoglicanos , Heparina/farmacologia , Heparitina Sulfato , Humanos , Compostos de Espiro , Proteínas do Envelope Viral
8.
Drug Discov Today ; 26(2): 542-550, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33181094

RESUMO

The spread of acquired drug resistance and of microorganisms naturally resistant to antibiotics is a major threat to global health, leading to an urgent need for novel antimicrobial compounds. Exogenous nitric oxide (NO) represents an attractive and promising antimicrobial approach, showing both bactericidal and biofilm dispersal activities. Numerous studies have been performed to develop NO donor scaffolds, including small molecules, macromolecular compounds, nanoparticles (NPs), and polymeric materials. This approach has resulted in successful outcomes, with some NO-releasing compounds entering clinical practice. In this review, we highlight the importance of this strategy, with a focus on lung infections.

9.
Eur J Med Chem ; 211: 113014, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33218683

RESUMO

Viruses are obligate intracellular parasites and have evolved to enter the host cell. To gain access they come into contact with the host cell through an initial adhesion, and some viruses from different genus may use heparan sulfate proteoglycans for it. The successful inhibition of this early event of the infection by synthetic molecules has always been an attractive target for medicinal chemists. Numerous reports have yielded insights into the function of compounds based on the dispirotripiperazine scaffold. Analysis suggests that this is a structural requirement for inhibiting the interactions between viruses and cell-surface heparan sulfate proteoglycans, thus preventing virus entry and replication. This review summarizes our current knowledge about the early history of development, synthesis, structure-activity relationships and antiviral evaluation of dispirotripiperazine-based compounds and where they are going in the future.


Assuntos
Antivirais/farmacologia , Desenho de Fármacos , Piperazinas/farmacologia , Compostos de Espiro/farmacologia , Vírus/efeitos dos fármacos , Antivirais/química , Proteoglicanas de Heparan Sulfato/antagonistas & inibidores , Proteoglicanas de Heparan Sulfato/metabolismo , Estrutura Molecular , Piperazinas/química , Compostos de Espiro/química , Vírus/metabolismo
10.
ACS Infect Dis ; 7(1): 88-100, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33352041

RESUMO

Latent Mycobacterium tuberculosis infection presents one of the largest challenges for tuberculosis control and novel antimycobacterial drug development. A series of pyrano[3,2-b]indolone-based compounds was designed and synthesized via an original eight-step scheme. The synthesized compounds were evaluated for their in vitro activity against M. tuberculosis strains H37Rv and streptomycin-starved 18b (SS18b), representing models for replicating and nonreplicating mycobacteria, respectively. Compound 10a exhibited good activity with MIC99 values of 0.3 and 0.4 µg/mL against H37Rv and SS18b, respectively, as well as low toxicity, acceptable intracellular activity, and satisfactory metabolic stability and was selected as the lead compound for further studies. An analysis of 10a-resistant M. bovis mutants disclosed a cross-resistance with pretomanid and altered relative amounts of different forms of cofactor F420 in these strains. Complementation experiments showed that F420-dependent glucose-6-phosphate dehydrogenase and the synthesis of mature F420 were important for 10a activity. Overall these studies revealed 10a to be a prodrug that is activated by an unknown F420-dependent enzyme in mycobacteria.


Assuntos
Tuberculose Latente , Mycobacterium tuberculosis , Tuberculose , Antituberculosos/farmacologia , Humanos , Mycobacterium tuberculosis/genética
11.
PLoS One ; 15(12): e0244010, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33296422

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0236630.].

12.
ACS Infect Dis ; 6(11): 3015-3025, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-32930569

RESUMO

Screening of a diversity-oriented compound library led to the identification of two 6,11-dioxobenzo[f]pyrido[1,2-a]indoles (DBPI) that displayed low micromolar bactericidal activity against the Erdman strain of Mycobacterium tuberculosis in vitro. The activity of these hit compounds was limited to tubercle bacilli, including the nonreplicating form, and to Mycobacterium marinum. On hit expansion and investigation of the structure activity relationship, selected modifications to the dioxo moiety of the DBPI scaffold were either neutral or led to reduction or abolition of antimycobacterial activity. To find the target, DBPI-resistant mutants of M. tuberculosis Erdman were raised and characterized first microbiologically and then by whole genome sequencing. Four different mutations, all affecting highly conserved residues, were uncovered in the essential gene rv0338c (ispQ) that encodes a membrane-bound protein, named IspQ, with 2Fe-2S and 4Fe-4S centers and putative iron-sulfur-binding reductase activity. With the help of a structural model, two of the mutations were localized close to the 2Fe-2S domain in IspQ and another in transmembrane segment 3. The mutant genes were recessive to the wild type in complementation experiments and further confirmation of the hit-target relationship was obtained using a conditional knockdown mutant of rv0338c in M. tuberculosis H37Rv. More mechanistic insight was obtained from transcriptome analysis, following exposure of M. tuberculosis to two different DBPI; this revealed strong upregulation of the redox-sensitive SigK regulon and genes induced by oxidative and thiol-stress. The findings of this investigation pharmacologically validate a novel target in tubercle bacilli and open a new vista for tuberculosis drug discovery.


Assuntos
Proteínas Ferro-Enxofre , Mycobacterium tuberculosis , Tuberculose , Humanos , Indóis , Proteínas Ferro-Enxofre/genética , Proteínas Ferro-Enxofre/metabolismo , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Oxirredução
13.
Sci Rep ; 10(1): 13205, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32764651

RESUMO

It is well-known that no local model-in theory-can simulate the outcome statistics of a Bell-type experiment as long as the detection efficiency is higher than a threshold value. For the Clauser-Horne-Shimony-Holt (CHSH) Bell inequality this theoretical threshold value is [Formula: see text]. On the other hand, Phys. Rev. Lett. 107, 170404 (2011) outlined an explicit practical model that can fake the CHSH inequality for a detection efficiency of up to 0.5. In this work, we close this gap. More specifically, we propose a method to emulate a Bell inequality at the threshold detection efficiency using existing optical detector control techniques. For a Clauser-Horne-Shimony-Holt inequality, it emulates the CHSH violation predicted by quantum mechanics up to [Formula: see text]. For the Garg-Mermin inequality-re-calibrated by incorporating non-detection events-our method emulates its exact local bound at any efficiency above the threshold. This confirms that attacks on secure quantum communication protocols based on Bell violation is a real threat if the detection efficiency loophole is not closed.

14.
PLoS One ; 15(8): e0236630, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745079

RESUMO

Quantum cryptography promises security based on the laws of physics with proofs of security against attackers of unlimited computational power. However, deviations from the original assumptions allow quantum hackers to compromise the system. We present a side channel attack that takes advantage of ventilation holes in optical devices to inject additional photons that can leak information about the secret key. We experimentally demonstrate light injection on an ID Quantique Clavis2 quantum key distribution platform and show that this may help an attacker to learn information about the secret key. We then apply the same technique to a prototype quantum random number generator and show that its output is biased by injected light. This shows that light injection is a potential security risk that should be addressed during the design of quantum information processing devices.

15.
Pathog Dis ; 78(7)2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-32860686

RESUMO

Influenza virus and coronaviruses continue to cause pandemics across the globe. We now have a greater understanding of their functions. Unfortunately, the number of drugs in our armory to defend us against them is inadequate. This may require us to think about what mechanisms to address. Here, we review the biological properties of these viruses, their genetic evolution and antiviral therapies that can be used or have been attempted. We will describe several classes of drugs such as serine protease inhibitors, heparin, heparan sulfate receptor inhibitors, chelating agents, immunomodulators and many others. We also briefly describe some of the drug repurposing efforts that have taken place in an effort to rapidly identify molecules to treat patients with COVID-19. While we put a heavy emphasis on the past and present efforts, we also provide some thoughts about what we need to do to prepare for respiratory viral threats in the future.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/epidemiologia , Coronavirus/efeitos dos fármacos , Reposicionamento de Medicamentos , Influenza Humana/epidemiologia , Orthomyxoviridae/efeitos dos fármacos , Pandemias , Anticoagulantes/uso terapêutico , Antimaláricos/uso terapêutico , Antioxidantes/uso terapêutico , Quelantes/uso terapêutico , Coronavirus/genética , Coronavirus/crescimento & desenvolvimento , Coronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Glicoconjugados/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Orthomyxoviridae/genética , Orthomyxoviridae/crescimento & desenvolvimento , Orthomyxoviridae/patogenicidade , Inibidores de Serino Proteinase/uso terapêutico
16.
Front Microbiol ; 11: 562, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32318042

RESUMO

There is an urgent need for new antimicrobials to treat the opportunistic Gram-negative Burkholderia cenocepacia, which represents a problematic challenge for cystic fibrosis patients. Recently, a benzothiadiazole derivative, C109, was shown to be effective against the infections caused by B. cenocepacia and other Gram-negative and-positive bacteria. C109 has a promising cellular target, the cell division protein FtsZ, and a recently developed PEGylated formulation make it an attractive molecule to counteract Burkholderia infections. However, the ability of efflux pumps to extrude it out of the cell represents a limitation for its use. Here, more than 50 derivatives of C109 were synthesized and tested against Gram-negative species and the Gram-positive Staphylococcus aureus. In addition, their activity was evaluated on the purified FtsZ protein. The chemical, metabolic and cellular stability of C109 has been assayed using different biological systems, including quantitative single-cell imaging. However, no further improvement on C109 was achieved, and the role of efflux in resistance was further confirmed. Also, a novel nitroreductase that can inactivate the compound was characterized, but it does not appear to play a role in natural resistance. All these data allowed a deep characterization of the compound, which will contribute to a further improvement of its properties.

17.
J Med Chem ; 63(17): 8917-8955, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32259446

RESUMO

Tuberculosis (TB) continues to claim the lives of around 1.7 million people per year. Most concerning are the reports of multidrug drug resistance. Paradoxically, this global health pandemic is demanding new therapies when resources and interest are waning. However, continued tuberculosis drug discovery is critical to address the global health need and burgeoning multidrug resistance. Many diverse classes of antitubercular compounds have been identified with activity in vitro and in vivo. Our analyses of over 100 active leads are representative of thousands of active compounds generated over the past decade, suggests that they come from few chemical classes or natural product sources. We are therefore repeatedly identifying compounds that are similar to those that preceded them. Our molecule-centered cheminformatics analyses point to the need to dramatically increase the diversity of chemical libraries tested and get outside of the historic Mtb property space if we are to generate novel improved antitubercular leads.


Assuntos
Antituberculosos/química , Mycobacterium tuberculosis/metabolismo , Antituberculosos/metabolismo , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Descoberta de Drogas , Farmacorresistência Bacteriana , Humanos , Mycobacterium tuberculosis/efeitos dos fármacos , Nitroimidazóis/química , Nitroimidazóis/metabolismo , Nitroimidazóis/farmacologia , Nitroimidazóis/uso terapêutico , Núcleosídeo-Fosfato Quinase/antagonistas & inibidores , Núcleosídeo-Fosfato Quinase/metabolismo , Relação Estrutura-Atividade , Tuberculose/tratamento farmacológico
18.
Molecules ; 25(6)2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32188089

RESUMO

Coxsackieviruses type B are one of the most common causes of mild upper respiratory and gastrointestinal illnesses. At the time of writing, there are no approved drugs for effective antiviral treatment for Coxsackieviruses type B. We used the core-structure of pleconaril, a well-known antienteroviral drug candidate, for the synthesis of novel compounds with O-propyl linker modifications. Some original compounds with 4 different linker patterns, such as sulfur atom, ester, amide, and piperazine, were synthesized according to five synthetic schemes. The cytotoxicity and bioactivity of 14 target compounds towards Coxsackievirus B3 Nancy were examined. Based on the results, the values of 50% cytotoxic dose (CC50), 50% virus-inhibiting dose (IC50), and selectivity index (SI) were calculated for each compound. Several of the novel synthesized derivatives exhibited a strong anti-CVB3 activity (SI > 20 to > 200). These results open up new possibilities for synthesis of further new selective anticoxsackievirus compounds.


Assuntos
Antivirais/farmacologia , Enterovirus Humano B/efeitos dos fármacos , Oxidiazóis/farmacologia , Oxazóis/farmacologia , Animais , Antivirais/síntese química , Antivirais/química , Morte Celular/efeitos dos fármacos , Chlorocebus aethiops , Cães , Células Madin Darby de Rim Canino , Oxidiazóis/síntese química , Oxidiazóis/química , Oxazóis/síntese química , Oxazóis/química , Piperazinas/síntese química , Piperazinas/química , Células Vero
19.
Front Microbiol ; 11: 292, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32158439

RESUMO

Tuberculosis remains one of the leading causes of death from a single pathogen globally. It is estimated that 1/4 of the world's population harbors latent tuberculosis, but only a 5-10% of patients will develop active disease. During latent infection, Mycobacterium tuberculosis can persist unaffected by drugs for years in a non-replicating state with low metabolic activity. The rate of the successful tuberculosis treatment is curbed by the presence of these non-replicating bacilli that can resuscitate after decades and also by the spread of M. tuberculosis drug-resistant strains. International agencies, including the World Health Organization, urge the international community to combat this global health emergency. The thienopyrimidine TP053 is a promising new antitubercular lead compound highly active against both replicating and non-replicating M. tuberculosis cells, with an in vitro MIC of 0.125 µg/ml. TP053 is a prodrug activated by the reduced form of the mycothiol-dependent reductase Mrx2, encoded by Rv2466c gene. After its activation, TP053 releases nitric oxide and a highly reactive metabolite, explaining its activity also against M. tuberculosis non-replicating cells. In this work, a new mechanism of TP053 resistance was discovered. M. tuberculosis spontaneous mutants resistant to TP053 were isolated harboring the mutation L240V in Rv0579, a protein with unknown function, but without mutation in Rv2466c gene. Recombineering method demonstrated that this mutation is linked to TP053 resistance. To better characterize Rv0579, the protein was recombinantly produced in Escherichia coli and a direct interaction between the Mrx2 activated TP053 and Rv0579 was shown by an innovative target-fishing experiment based on click chemistry. Thanks to achieved results, a possible contribution of Rv0579 in M. tuberculosis RNA metabolism was hypothesized, linked to toxin anti-toxin system. Overall, these data confirm the role of Rv0579 in TP053 resistance and consequently in the metabolism of this prodrug.

20.
Eur J Med Chem ; 190: 112132, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32066012

RESUMO

Cystic fibrosis is a rare genetic disease characterized by the production of dehydrated mucus in the lung able to trap bacteria and rendering their proliferation particularly dangerous, thus leading to chronic infections. Among these bacteria, Staphylococcus aureus and Pseudomonas aeruginosa play a major role while, within emerging pathogens, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, Burkholderia cepacia complex species, as well as non-tuberculous mycobacteria are listed. Since a common feature of these bacteria is the high level of drug resistance, cell division, and in particular FtsZ, has been explored as a novel therapeutic target for the design of new molecules with antibacterial properties. This review summarizes and provides insight into recent advances in the discovery of compounds targeting FtsZ: the majority of them exhibit anti-staphylococcal activity, while a few were directed against the cystic fibrosis Gram negative pathogens.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas do Citoesqueleto/antagonistas & inibidores , Antibacterianos/química , Antibacterianos/uso terapêutico , Fibrose Cística/microbiologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , GTP Fosfo-Hidrolases/antagonistas & inibidores , Bactérias Gram-Negativas/efeitos dos fármacos , Humanos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos
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