Plakinamine P, A Steroidal Alkaloid with Bactericidal Activity against .

Tuberculosis is the leading cause of death due to infectious disease worldwide. There is an urgent need for more effective compounds against this pathogen to control the disease. Investigation of the anti-mycobacterial activity of a deep-water sponge of the genus revealed the presence of a new steroidal alkaloid of the plakinamine class, which we have given the common name plakinamine P.

Evidence for Inhibition of Topoisomerase 1A by Gold(III) Macrocycles and Chelates Targeting Mycobacterium tuberculosis and Mycobacterium abscessus.

and the fast-growing species are two important human pathogens causing persistent pulmonary infections that are difficult to cure and require long treatment times. The emergence of drug-resistant strains and the high level of intrinsic resistance of call for novel drug scaffolds that effectively target both pathogens. In this study, we evaluated the activity of bis(pyrrolide-imine) gold(III) macrocycles and chelates, originally designed as DNA intercalators capable of targeting human topoisomerase types I and II (Topo1 and Topo2), against and We identified a total of 5 noncytotoxic compounds active against both mycobacterial pathogens under replicating conditions.

Selective Killing of Dormant Mycobacterium tuberculosis by Marine Natural Products.

The dormant phenotype acquired by during infection poses a major challenge in disease treatment, since these bacilli show tolerance to front-line drugs. Therefore, it is imperative to find novel compounds that effectively kill dormant bacteria. By screening 4,400 marine natural product samples against dual-fluorescent under both replicating and nonreplicating conditions, we have identified compounds that are selectively active against dormant This validates our strategy of screening all compounds in both assays as opposed to using the dormancy model as a secondary screen.

Dragmacidin G, a Bioactive Bis-Indole Alkaloid from a Deep-Water Sponge of the Genus Spongosorites.

A deep-water sponge of the genus has yielded a bis-indole alkaloid which we have named dragmacidin G. Dragmacidin G was first reported by us in the patent literature and has recently been reported by Hitora et al. from a sponge of the genus .

Small-Molecule Inhibitors Targeting Topoisomerase I as Novel Antituberculosis Agents.

Bacterial topoisomerase functions are required for regulation of DNA supercoiling and overcoming the DNA topological barriers that are encountered during many vital cellular processes. DNA gyrase and topoisomerase IV of the type IIA bacterial topoisomerase family are important clinical targets for antibacterial therapy. Topoisomerase I, belonging to the type IA topoisomerase family, has recently been validated as a potential antitubercular target.