title: 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.
authors.affiliation: Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodzki St., PL-20093 Lublin. Poland.
authors.forename: Agnieszka A
authors.initials: AA
authors.lastname: Kaczor
authors.affiliation: Department of Applied Pharmacy, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 1 Chodzki St., PL-20093 Lublin. Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Polski
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy with Division of Medical Analytics, 4A Chodzki St., PL-20093 Lublin. Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Sobótka-Polska
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy with Division of Medical Analytics, 4A Chodzki St., PL-20093 Lublin. Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Pachuta-Stec
authors.affiliation: Department of Inorganic Chemistry, Faculty of Chemistry, M. Curie-Sklodowska University, M. Curie-Sklodowska Sq. 2, PL-20031 Lublin. Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Makarska-Bialokoz
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy with Division of Medical Analytics, 4A Chodzki St., PL-20093 Lublin. Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Pitucha
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods*; D024881:Drug Resistance, Bacterial; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D010457:Peptidoglycan / Q000378:metabolism; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D010457:Peptidoglycan
keywords: Antibacterial activity; antibacterial compounds; antibacterial drug target; antibiotics resistance; infectious
  diseases treatment; structure-activity relationship