Kidwai M, Sapra P, Bhushan K R
Department of Chemistry, University of Delhi, Delhi, 110007, India.
Curr Med Chem. 1999 Mar;6(3):195-215.
More than five decades since the Discovery of Penicillin, the chemistry and biological activity of b-lactams continue to attract the wide spread attention of research workers. Owing to high efficacy and extremely safe toxicological profile, they are agents of choice in the current therapeutic index for the bacterial infectious diseases. Tremendous efforts have been made into synthesis and structural modification of the beta-lactam nucleus to increase antimicrobial activity and pharmacokinetic performance. These efforts resulted in the development of ampicillin, amoxicillin and a group of cephalosporins as clinically effective therapeutic agents. However the rapid emergence of bacterial strains resistant to most generally used members of this class of compound stimulated research for novel beta-lactams, stable to beta-lactamase and possess high potency, broad spectrum of activity both in vitro and in vivo. The mode of action of beta-lactams is to inhibit an enzyme transpeptidase , penicillin binding proteins, critical in the production of bacterial cell wall.
自青霉素被发现五十多年来，β-内酰胺类药物的化学性质和生物活性一直吸引着研究人员的广泛关注。由于其高效性和极低的毒理学特性，它们是当前治疗细菌感染性疾病治疗指数中的首选药物。人们为β-内酰胺核的合成和结构修饰付出了巨大努力，以提高抗菌活性和药代动力学性能。这些努力促成了氨苄西林、阿莫西林以及一组头孢菌素作为临床有效治疗药物的开发。然而，对这类化合物中最常用成员产生耐药性的细菌菌株迅速出现，这刺激了对新型β-内酰胺类药物的研究，这些药物对β-内酰胺酶稳定，并且在体外和体内都具有高效、广谱的活性。β-内酰胺类药物的作用方式是抑制一种转肽酶，即青霉素结合蛋白，它对细菌细胞壁的产生至关重要。
