Tetracyclines: Nonantibiotic properties and their clinical implications

Sapadin, Allen N.; Fleischmajer, Raúl

doi:10.1016/j.jaad.2005.10.004

Cited by 640 publications

(464 citation statements)

References 80 publications

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“…Metastat has limited systemic toxicity and lacks the antimicrobial activity (Lokeshwar et al, 2001) because of the removal of the dimethyl amino group (Hidalgo and Eckhardt, 2001). Mode of inhibition of MMP activity is by binding to metal ions such as Zn 2+ (Sapadin and Fleischmajer, 2006).…”

Section: Tetracycline Derivativesmentioning

confidence: 99%

Matrix Metalloproteinases and Cancer - Roles in Threat and Therapy

Yadav¹,

Puri²,

Rastogi³

et al. 2014

Asian Pacific Journal of Cancer Prevention

187

131

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Matrix metalloproteinases (MMPs) are a family of zinc dependent extracellular matrix (ECM) remodelling endopeptidases having the ability to degrade almost all components of extracellular matrix and implicated in various physiological as well as pathological processes. Carcinogenesis is a multistage process in which alteration of the microenvironment is required for conversion of normal tissue to a tumour. Extracellular matrix remodelling proteinases such as MMPs are principal mediators of alterations observed in the microenvironment during carcinogenesis and according to recent concepts not only have roles in invasion or late stages of cancer but also in regulating initial steps of carcinogenesis in a favourable or unfavourable manner. Establishment of relationships between MMP overproduction and cancer progression has stimulated the development of inhibitors that block proteolytic activity of these enzymes. In this review we discuss the MMP general structure, classification, regulation roles in relation to hallmarks of cancer and as targets for therapeutic intervention.

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Section: Tetracycline Derivativesmentioning

confidence: 99%

Matrix Metalloproteinases and Cancer - Roles in Threat and Therapy

Yadav¹,

Puri²,

Rastogi³

et al. 2014

Asian Pacific Journal of Cancer Prevention

187

131

View full text Add to dashboard Cite

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“…Consistent with that interpretation, antibiotics reduce the rate of aseptic loosening [10,23] and periprosthetic inflammation [89] in patients as well as particle-induced osteolysis in mice [91]. However, those results do not conclusively support the PAMP hypothesis because antibiotics can have antiinflammatory effects that are independent of their bactericidal effects [58,61,90,94]. The PAMP hypothesis depends on the presence of these molecules, at least episodically, during aseptic loosening.…”

Section: Toll-like Receptorsmentioning

confidence: 99%

“…3) and whether the reported effects of antibiotics on aseptic loosening [10,23,89,91] are the result of bactericidal effects or the antiinflammatory effects of antibiotics that are independent of bacteria [58,61,90,94]. Further in vivo murine studies are also needed to determine (1) whether PAMPs are required for TLR activation; (2) the roles of pathogen recognition receptors other than TLR2 and TLR4; and (3) the mechanisms responsible for particle-induced osteolysis in the absence of PAMPs.…”

Section: Where Do We Need To Go?mentioning

confidence: 99%

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Greenfield

2014

Clin Orthop Relat Res

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Background Overwhelming evidence supports the concept that wear particles are the primary initiator of aseptic loosening of orthopaedic implants. It is likely, however, that other factors modulate the biologic response to wear particles. This review focuses on three potential other factors: genetic susceptibility, Toll-like receptors (TLRs), and bacterial pathogen-associated molecular patterns (PAMPs). Where Are We Now? Considerable evidence is emerging that both genetic susceptibility and TLR activation are important factors that modulate the biologic response to wear particles, but it remains controversial whether bacterial PAMPs also do so. Where Do We Need to Go? Detailed understanding of the roles of these other factors may lead to identification of novel therapeutic targets for patients with aseptic loosening. How Do We Get There? Highest priority should be given to polymorphism replication studies with large numbers of patients and studies to replicate the reported correlation between bacterial biofilms and the severity of aseptic loosening.

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“…31 É interessante comentar que tetraciclinas possuem uma série de propriedades não antibióticas e há vários estudos sendo conduzidos no sentido de se usar tetraciclinas no tratamento de doenças não infecciosas, tais como artrite reumatoide e câncer. [32][33][34][35][36][37] Curiosamente, apesar de tetraciclinas serem bons agentes complexantes, não há na literatura relatos de complexos destes ligantes com alguns metais considerados importantes do ponto de vista farmacológico, como exemplo, ouro, bismuto e prata. 38 Com relação às propriedades bio- lógicas exibidas pelos complexos metálicos contendo tetraciclinas, as pesquisas indicam que estes compostos são bons pontos de partida no que se refere ao desenvolvimento de novos agentes antitumorais e antimicrobianos.…”

Section: Coordenação De Metais a Tetraciclinasunclassified

Coordenação de metais a antibióticos como uma estratégia de combate à resistência bacteriana

Rocha¹,

Pinto²,

Ruggiero³

et al. 2011

Quím. Nova

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Recebido em 12/1/10; aceito em 2/8/10; publicado na web em 16/11/10 COORDINATION OF METALS TO ANTIBIOTICS AS A STRATEGY TO COMBAT BACTERIAL RESISTANCE. Antibiotic resistance has been growing at an alarming rate and consequently the arsenal of effective antibiotics against Gram-negative and Gram-positive bacteria has dropped dramatically. In this sense there is a strong need to produce new substances that not only have good spectrum of activity, but having new mechanisms of action. In this regard, this paper emphasizes the coordination of metals to antibiotics as a strategy for reversing antibiotic resistance and production of new drugs, with a special focus on quinolones, fluoroquinolones, sulfonamides and tetracyclines.Keywords: antibiotics; metal-based drugs; bacterial resistance. INTRODUÇÃOA descoberta dos antibióticos representa um dos mais importantes marcos da medicina moderna. A introdução das sulfonamidas em 1930 e da penicilina na década posterior provocaram um grande avanço no tratamento de doenças infecciosas, causando uma drásti-ca diminuição nas taxas de mortalidade e uma enorme sensação de bem-estar. 1 O sucesso dos primeiros antibióticos na cura de doenças até então consideradas letais acarretou uma intensa busca por novas drogas. De fato, as décadas de 40, 50 e 60 do século passado foram marcadas pela imensa quantidade de antibióticos produzidos e rapidamente incorporados às práticas clínicas. 2 No entanto, nas décadas posteriores houve um declínio na produção destes compostos. Entre o lançamento das quinolonas em 1962 até a aprovação das oxazolidinonas em 2000, houve pouca inovação no que se refere à introdução de novas classes de antibióticos de uso clínico bem-sucedido. 2 Quando um antibiótico é descoberto e introduzido no mercado, sua utilidade clínica começa a diminuir até um ponto em que há um aumento na restrição de seu uso. Esta restrição é provocada pelo surgimento de cepas resistentes. As bactérias surgiram na terra há bilhões de anos e para sobreviver desenvolveram mecanismos de resistência aos antibióticos que são encontrados livres na natureza. 3 Portanto, não é surpreendente o fato de que muitos antibióticos lançados nas últimas décadas, que são em sua ampla maioria de origem natural ou semissintética, terem utilidade limitada na época de sua descoberta e em pouco tempo se tornarem obsoletos. 3 Outro fator que contribui muito para tornar um antibiótico menos eficiente é a sua utilização indiscriminada e incorreta, o que vem a favorecer o surgimento de micro-organismos resistentes. Atualmente, algumas classes de micro-organismos representam extrema preocupação para a saúde publica. Dentre os que mais provocam mortes no mundo estão o Staphylococcus aureus meticilina-resistente (MRSA), Staphylococcus aureus vancomicina-resistente (VRSA), Escherichia coli, Klebsiella pneumoniae e Pseudomonas aeruginosa, que são bactérias resistentes a múltiplas drogas. Os processos infecciosos causados por estas classes de micro-organismos geralmente estão associados com alta letalidade e altos custos d...

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Tetracyclines: Nonantibiotic properties and their clinical implications

Cited by 640 publications

References 80 publications

Matrix Metalloproteinases and Cancer - Roles in Threat and Therapy

Matrix Metalloproteinases and Cancer - Roles in Threat and Therapy

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Coordenação de metais a antibióticos como uma estratégia de combate à resistência bacteriana

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