Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis.

Tuberculosis (TB) is responsible for enormous global morbidity and mortality, and current treatment regimens rely on the use of drugs that have been in use for more than 40 years. Owing to widespread resistance to these therapies, new drugs are desperately needed to control the TB disease burden. Herein, we describe the rapid synthesis of analogues of the sansanmycin uridylpeptide natural products that represent promising new TB drug leads. The compounds exhibit potent and selective inhibition of Mycobacterium tuberculosis, the etiological agent of TB, both in vitro and intracellularly. The natural product analogues are nanomolar inhibitors of Mtb phospho-MurNAc-pentapeptide translocase, the enzyme responsible for the synthesis of lipid I in mycobacteria. This work lays the foundation for the development of uridylpeptide natural product analogues as new TB drug candidates that operate through the inhibition of peptidoglycan biosynthesis.

A strategy for controlling potential interactions between natural health products and chemotherapy: a review in pediatric oncology.

The high prevalence of complementary and alternative medicine use including natural health products (NHPs) in the pediatric oncology population is well established. The potential for concurrent use of NHPs with conventional chemotherapy necessitates physician awareness regarding the potential risks and benefits that might come from this coadministration. Knowledge of interactions between NHPs and chemotherapy is poorly characterized; however, an understanding of potential mechanisms of interaction by researchers and clinicians is important. Concerns regarding the use of antioxidants during chemotherapy are controversial and evidence exists to support both adherents and detractors in this debate. Our review addresses issues regarding potential interactions between NHPs and chemotherapies used in pediatric oncology from a pharmacokinetic and pharmacodynamic perspective. Examples of combinations of NHP and chemotherapies are briefly presented in addition to a strategy to avoid (or induce) a possible interaction between a NHP and chemotherapy. In conclusion, more clinical research is needed to substantiate or preclude the use of NHPs in the treatment of cancer and especially in combination with chemotherapy.