Beta-lactams and their potential use as novel anticancer chemotherapeutics drugs.
The discovery of natural and synthetic antibiotics is one of the most important medical breakthroughs in human history. Many diseases, such as bacterial meningitis, pneumonia, and septicemia, are now curable with the use of antibiotics. Antibiotics are efficacious, generally well tolerated in patients, and have a low toxicity level. It is for these reasons antibiotics remain an attractive target for drug discovery. Traditional beta-lactam antibiotics (e.g. penicillins, penems, cephalosporins) have a bicyclic ring structure that is conformationally rigid and functions to inhibit bacterial cell wall synthesis. In addition to the bactericidal action of antibiotics, it has been discovered that many antibiotics are capable of inhibiting tumor cell growth. There are currently many antitumor antibiotics approved for cancer therapy, which work to inhibit tumor cell growth by DNA intercalation. The use of beta-lactams as prodrugs has also met with success by aiding delivery of the chemotherapeutic directly to tumor sites. Recently, a novel class of N-thiolated monobactams, so termed because they possess a monocyclic ring instead of the bicyclic ring, has been found to induce apoptosis potently and specifically in many tumor cell lines but not in normal, non-transformed cell lines. Other beta-lactams, such as the polyaromatics, have been found to slow or inhibit tumor cell growth, and the 4-alkylidene beta-lactams are capable of inhibiting matrix metalloproteinases and leukocyte elactase activity. These data indicate that synthesis and evaluation of beta-lactams are a promising area for further development in anticancer research.
Kuhn
Deborah
D
The Prevention Program, Barbara Ann Karmanos Cancer Institute, and Department of Pathology, School of Medicine, Wayne State University, Detroit, Michigan, USA.
Coates
Cristina
C
Daniel
Kenyon
K
Chen
Di
D
Bhuiyan
Mohammad
M
Kazi
Aslamuzzaman
A
Turos
Edward
E
Dou
Q Ping
QP
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D015195:Drug Design; D006801:Humans; D007364:Intercalating Agents / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy*; D011355:Prodrugs / Q000494:pharmacology; D016499:Radioimmunotherapy; D047090:beta-Lactams / Q000737:chemistry* / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D007364:Intercalating Agents; D011355:Prodrugs; D047090:beta-Lactams; D004247:DNA