Novel Antibacterial Compounds and their Drug Targets - Successes and Challenges

Abstract

Infectious diseases are one of the most important and urgent health problems in the world. According to the World Health Organization (WHO) statistics, infectious and parasitic diseases are a cause of about 16% of all deaths worldwide and over 40% of deaths in Africa. A considerable progress that has been made during last hundred years in the fight against infectious diseases, in particular bacterial infections, can be attributed mainly to three factors: (1) the general improvement of living conditions, in particular sanitation; (2) development of vaccines and (3) development of efficient antibacterial drugs. Although considerable progress in reduction of the number of cases of bacterial infections, especially in lethal cases, has been made, continued cases and outbreaks of these diseases persist, which is caused by different contributing factors. Indeed, during last sixty years antibacterial drugs were used against various infectious diseases caused by bacterial pathogens with an undoubtable success. The most fruitful period for antibiotic development lasted from 40's to 60's of the last century and resulted in the majority of antibiotics currently on the market, which were obtained by screening actinomycetes derived from soil. Although the market for antibacterial drugs is nowadays greater than 25 billion US dollars per year, novel antibacterial drugs are still demanded due to developed resistance of many pathogenic bacteria against current antibiotics. In the last five years, one can observe a dramatic increase in cases of resistant bacteria strains (e.g. Klebsiella pneumoniae and E. coli) which are responsible for difficult to treat pneumonia and infections of urinary tract. The development of resistant bacteria strains is a side effect of antibiotic application for treatment: the infections become untreatable as a result of the existence of antibiotic-tolerant persisters. In this review, we discuss the challenges in antibacterial drug discovery, including the molecular basis of drug resistance, drug targets for novel antibacterial drugs, and new compounds (since year 2010) from different chemical classes with antibacterial activity, focusing on structure-activity relationships.

Antimicrobial Peptides and Nanotechnology, Recent Advances and Challenges

“…At the same time as AMPs emerge as a new antimicrobial therapeutic, resistance to available antibiotics has become a worldwide problem ( Kaczor et al, 2017 ). Thus, as favorable possibilities, the use of AMPs has been studied not only against susceptible pathogens, but also against persistent bacteria and fungi ( Jiang et al, 2014 ; Stedt et al, 2014 ).…”

Evaluation of potassium clavulanate supplementation of Bolton broth for enrichment and detection of Campylobacter from chicken

“…In addition, the E . coli may express molecules killing competing bacteria including antimicrobial peptides, type VI secretion systems, or toxic proteins [ 23 , 24 ]. Further studies are required to test these hypotheses and reach conclusions.…”

Synthesis and evaluation of antimicrobial and anticancer activities of 3‐phenyl‐1‐phenylsulfonyl pyrazoles containing an aminoguanidine moiety

“…Although considerable progress in the treatment of bacterial infections has been made in the past few decades, bacterial diseases persist, and bacterial resistance rises. [1][2][3] Drugresistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, multidrug-resistant Escherichia coli, and multidrug-resistant Pseudomonas aeruginosa, cause lethal diseases and great difficulties in the treatment of communityacquired and nosocomial infections, [4][5][6][7] which have become a severe threat for global public health. [8][9][10] Nowadays, the global market for antimicrobial drugs is greater than 25 billion U.S. dollars per year, and various strategies and targets have been studied to relieve bacterial infections.…”

“…Yield 24%; m.p. 180-182°C 1. H NMR (DMSO-d 6 , 300 MHz): δ 2.29 (s, 3H, CH 3 ), 2.39 (s, 3H, CH 3 ), 7.13 (d, 2H, J = 7.7 Hz, Ph-H), 7.29-7.61 (m, 12H, Ar-H, guanidyl-H), 7.93 (d, 2H, J = 7.7 Hz, Ph-H), 8.02 (s, 1H, CH══N), 9.12 (s, 1H, NH), 11.91 (s, 1H, PhSO 2 H).…”