Lack of development of new antimicrobial drugs: a potential serious threat to public health

The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria

“…However, with the limited accuracy of the measurements and the poor knowledge of molecular parameters, this simplified model might satisfy most of the current needs. Inserting experimental values -for example, for ampicillin permeating through OmpF k on ≈ 10 4 [Ms] -1 (moles per litre per second) and K ≈ 1 [Ms] -1 -provides about 10 molecules per second per monomer under a 1 mM concentration gradient. It is important to note that diffusion will bring about 10 5 molecules into the vicinity of the channel entrance, but only 0.1% of these molecules are effectively translocated.…”

“…In a second step, transition state theory accounts for the energy gain that is observed owing to the presence of an affinity pocket in the channel and relates this to the kinetics of permeation. The transition state theory provides Equation 4.…”

“…Moreover, no truly novel active antibacterial compound is currently in clinical trials. Thus, it is important to decipher the molecular basis of the MDR mechanisms [3][4][5] . MDR is prevalent in key Gram-negative clinical pathogens, such as Escherichia coli, Salmonella spp., Klebsiella spp., Enterobacter spp., Campylobacter spp., Acinetobacter spp.…”

The Evolution of Drug Development in Schizophrenia: Past Issues and Future Opportunities

“…The treatment discovery process has produced a series of drugs acting at the D2 receptor, and no drug has been approved for marketing with a novel molecular target. This has been noted as a general problem for the pharmaceutical industry (Drews, 2000;Dutta and Garner, 2003;Mills, 2006;Norrby et al, 2005;Carpenter, 2004;Scolnick, 2004;Korn and Stanski, 2005) and applies also to developing drugs for depression and other mental illnesses.…”

Otimização do processo fermentativo para produção do antibiótico nigericina por Streptomyces

“…Apesar do sucesso da descoberta de novos antibióticos, e os avanços no processo de sua produção, as doenças infecciosas continuam sendo a segunda principal causa de morte no mundo, causando aproximadamente 17 milhões de mortes por ano, afetando principalmente crianças e idosos. 6,7 Apesar dos produtos naturais serem uma fonte promissora, a descoberta e o desenvolvimento de novas drogas antibióticas por grandes empresas farmacêuticas, têm diminuído ao longo das últimas duas décadas. As empresas com programas de descoberta de novos antibióticos estão diminuído gradualmente esses esforços.…”