1. Simulating the inhibition reaction of Mycobacterium tuberculosis L,D-transpeptidase 2 by carbapenems
JoseRogerio A. Silva, Thavendran Govender, Adrian E. Roitberg*, Claudio Nahum Alves*. Chem. Commun., 2015, 51, 12560—12562
The LDT enzymes are eﬃciently inhibited by carbapenems, such as meropenem, imipenem, doripenem and ertapenem. Carbapenems form an extremely important class of antibiotic β-lactam compounds. Among hundreds of diﬀerent b-lactams, carbapenems exhibit a wide spectrum of activities with the strongest potency against Gram-negative and Gram-positive bacteria. Developing carbapenems for the treatment of tuberculosis disease has raised wide interest since these compounds, in association with clavulanic acid as a b-lactamase inhibitor, are even active against extensively drug-resistant Mtb (XDR-TB).
2. Natural products to drugs: natural product-derived compounds in clinical trials
Mark S. Butler*. Nat. Prod. Rep., 2008, 25, 475–516
Doripenem (Finibax , Doribax ) 4 is a synthetic carbapenem-type b-lactam that was launched in 2005 in Japan by Shionogi & Co. as a broad-spectrum antibiotic. The ﬁrst carbapenem to be identiﬁed was the actinomycete-derived NP thienamycin 5. Johnson & Johnson (J&J) (formerly Peninsula Pharmaceuticals) obtained formal FDA approval in October 2007 for use of doripenem 4 in the treatment of complicated intra-abdominal and complicated urinary tract infections, including pyelonephritis. The use of doripenem 4 for treatment of hospital-acquired (nosocomial) pneumonia (HAP) is under FDA review, while in Europe treatment of HAP and complicated urinary tract infections are under review. Other carbapenems undergoing clinical evaluation are described in Section 3.1.