Diversity-oriented synthesis of furo[3,2-f]chromanes with antimycobacterial activity
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The transketolase (TKT) enzyme in Mycobacterium tuberculosis represents a novel drug target for tuberculosis treatment and has low homology with the orthologous human enzyme. Here, we report on the structural and kinetic characterization of the transketola ...
Benzothiazinones (BTZs) form a new class of potent antimycobacterial agents. Although the target of BTZs has been identified as decaprenylphosphoryl-β-D-ribose 2'-epimerase (DprE1), their detailed mechanism of action remains obscure. Here we demonstrate th ...
The exact role of the DosR "dormancy" regulon in the pathogenesis of Mycobacterium tuberculosis is still unclear. It has been observed that members of the regulon, including dosR, are constitutively expressed in clinical isolates belonging to the W/Beijing ...
Atropisomers as well as CC2 epimers of complestatin and chloropeptin I are readily synthesized through an intramol. SNAr reaction and the Suzuki-Miyaura reaction. The abs. configuration of amino acid N-methyl-2-(3,5-dichloro-4-hydroxyphenyl)glycine was fou ...
The new antitubercular drug candidate 2-[2-S-methyl-1,4-dioxa-8-azaspiro[4.5]dec-8-yl]-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one (BTZ043) targets the DprE1 (Rv3790) subunit of the enzyme decaprenylphosphoryl-beta-d-ribose 2'-epimerase. To monit ...
Tuberculosis is still a leading cause of death in developing countries and a resurgent disease in developed countries. The selection and soaring spread of Mycobacterium tuberculosis multidrug-resistant (MDR-TB) and extensively drug-resistant strains (XDR-T ...
A concise total synthesis of arylomycin A2 was accomplished featuring a key intramol. Suzuki-Miyaura reaction for the formation of the 14-membered meta,meta-cyclophane and direct coupling of a fully elaborated peptide side-chain with the macrocyclic core. ...
Background: The variable efficacy (0-80%) of Mycobacterium bovis Bacille Calmette Gurein (BCG) vaccine against adult tuberculosis (TB) necessitates development of alternative vaccine candidates. Development of recombinant BCG (rBCG) over-expressing promisi ...
We recently reported that 3,3-dimethyl-3H-benzofuro[3,2,f][1]-benzopyran and its hydrogenated analogue are selective in vitro inhibitors of mycobacterial growth. However, their lack of in vivo activity on a murine model of Mycobacterium tuberculosis infect ...
Discovering new drugs to treat tuberculosis more efficiently and to overcome multidrug resistance is a world health priority. To find antimycobacterial scaffolds, we screened a kinase inhibitor library of more than 12,000 compounds using an integrated stra ...