A General Review of Tetracyclines Antibiotics
A General Review of Tetracyclines Antibiotics
Chang Liu
Instructor: Prof. Jasson Sello
Department of Chemistry, Brown University
Providence 02906, RI
Tetracyclines are the first broad-spectrum antibiotic to be applied to clinic use. Nevertheless, the increasing incidence of bacterial resistance of tetracyclines led to a series of studies on the development of semisynthetic tetracyclines to circumvent the resistant organisms. In order to better design the structures of tetracycline derivatives, research on the action mode of tetracyclines, mechanisms of resistance, biosynthesis and total synthesis of tetracyclines were also performed.
Keywords: Tetracyclines, Structure-activity Relationship, Mode of Action,
Mechanisms of Resistance, Biosynthesis, Total Synthesis
1. Introduction
Tetracyclines are a group of polyketide broad-spectrum antibiotics that has activity against a variety of gram-positive and gram-negative bacteria, mycoplasmas, chlamydiae and peotozoan parasites [1]. The discovery of tetracycline was in the 1940s. At that time, the problems related to the production of Pennicillin has been solved and pharmaceutical industry
and academic institutes started to concentrate their energy on the development of new antibiotics. In 1948, the first member of tetracycline family—chlorotetracyclin, or Aureomycin was discovered as an isolate of
Streptomyces Aureofaciens in an antibiotic screening program functioned in Lederle Labs [2]. In 1950, oxytetracycline or Terramycin—second member of tetracycline was found as a metabolite of Streptomyces rimosus by Finlay et al. [3] and the chemical structure of oxytetracycline was defined by Woodward, which was a hallmark in tetracycline research.
Since then, tetracyclines has been intensively used in both human therapy and animal feed use [4]. They have been extensively applied to human therapy for treatment of bacterial respiratory and urogenital diseases, as well as periodontal, Lyme, and
Chang Liu
Instructor: Prof. Jasson Sello
Department of Chemistry, Brown University
Providence 02906, RI
Tetracyclines are the first broad-spectrum antibiotic to be applied to clinic use. Nevertheless, the increasing incidence of bacterial resistance of tetracyclines led to a series of studies on the development of semisynthetic tetracyclines to circumvent the resistant organisms. In order to better design the structures of tetracycline derivatives, research on the action mode of tetracyclines, mechanisms of resistance, biosynthesis and total synthesis of tetracyclines were also performed.
Keywords: Tetracyclines, Structure-activity Relationship, Mode of Action,
Mechanisms of Resistance, Biosynthesis, Total Synthesis
1. Introduction
Tetracyclines are a group of polyketide broad-spectrum antibiotics that has activity against a variety of gram-positive and gram-negative bacteria, mycoplasmas, chlamydiae and peotozoan parasites [1]. The discovery of tetracycline was in the 1940s. At that time, the problems related to the production of Pennicillin has been solved and pharmaceutical industry
and academic institutes started to concentrate their energy on the development of new antibiotics. In 1948, the first member of tetracycline family—chlorotetracyclin, or Aureomycin was discovered as an isolate of
Streptomyces Aureofaciens in an antibiotic screening program functioned in Lederle Labs [2]. In 1950, oxytetracycline or Terramycin—second member of tetracycline was found as a metabolite of Streptomyces rimosus by Finlay et al. [3] and the chemical structure of oxytetracycline was defined by Woodward, which was a hallmark in tetracycline research.
Since then, tetracyclines has been intensively used in both human therapy and animal feed use [4]. They have been extensively applied to human therapy for treatment of bacterial respiratory and urogenital diseases, as well as periodontal, Lyme, and
References: [1] Chopra, I.; Roberts, M. Microbiology and Molecular Biology Reviews , 232 (2001). [2] Duggar, B.M. Ann. NY Acad. Sci. 51, 177 (1948). [3] Finlay, A.C. Science 111, 85 (1950). [5] Roberts, M.C. FEMS Microbiol. Lett. 245, 195 (2005). [6] Hlavka, J.J.; Boothe J.H. Handbook of experimental pharmacology 78, 179 (1985). [7] Agwuh, K.N.; MacGowan, A. J. Antimicrob. Chemother. 58, 256 (2006). [8] Bahrami, F.; Morris, D.L. Pourgholami, M.H., Mini-Reviews in Medicinal Chemistry 12, 44 (2012). [9] Doerschuk, A.P.; Bitler, B.A. J. Am. Chem. Soc. 77, 4687 (1955). 20, 539 (1968). [11] McMurry, L.M., et al. Antimicrob. Agents Chemother. 22, 791 (1982). [13] Chopra, I. Antimicrob. Chemother. 38, 637 (1994). [14] George, A.P. J. Antimicrobial Chemotherapy 56, 470 (2005). [15] Argast, M.; Beck, C.F. Antimicrob. Agents Chemother. 141, 260 (1985). [16] Nikaido, H.; Thanassi, D.G. Antimicrob. Agents Chemother. 37, 1393 (1993). [17] Rudolf, O.; Norbert, P.; Andrea, B. Nucleic Acids Research 25, 1219 (1997). [18] Epe, B.; Wooley, P.; Hornig, H. FEBS Lett. 213, 443 (1987). 16, 1218 (1988). [20] Roberts, M. FEMS Microbiol. Rev. 19, 1 (1996). [22] Lauren, B.P.; Tang, Y. Metabolic Engineering 11, 69 (2009). [23] Korst, J.J. et al. J. Am. Chem. Soc. 90, 439 (1968). 118, 5304 (1996). [26] Charest, M.G. et al. Science 308, 15 (2005).