Drug-Resistant Tuberculosis (DR-TB) is a major contagious disease which seriously threatens the human health. It is significantly meaningful to develop novel anti-DR TB drugs with new mechanisms of action.
Prof. Huang’s group has been dedicating in the research of novel anti-DR TB drugs since 2007. Recently, collaborated with Dr. Gurdyal S. Besra’s Group in University of Birmingham (UOB), a series of novel thiophene-arylamide derivatives targeting DprE1 which is crucial for mycobacterial cell wall biosynthesis, was identified through a structure-based scaffold hopping strategy. The representative compound 25a is worthy of further development as a non-covalent DprE1 inhibitor with promising druggability. The related work was published as a cover paper in the Journal of Medicinal Chemistry in May, 2021. Dr. Pengxu Wang in IMM and Dr. Sarah M. Batt in UOB were the co-first authors. Prof. Gang Li, Prof. Haihong Huang in IMM and Prof. Gurdyal S. Besra in UOB were the co-corresponding authors.
In addition, Huang’s group has conducted lots of research on the discovery of novel oxazolidinones as anti-DR TB drugs. A series of conformationally constrained novel benzo[1,3]oxazinyl-oxazolidinones were designed and synthesized. Compound 20aa as a novel potential antibacterial with an excellent PK profile, displayed good to excellent antibacterial activity in vitro including against drug-resistant TB strains, MRSA, MRSE, VISA and VRE. The related work was published in the Journal of Medicinal Chemistry in March, 2021. Dr. Yongqi Wu was the first author. Prof. Dongfeng Zhang, Prof. Haihong Huang in IMM and Prof. Ning Sun in Guangzhou Medical University were the co-corresponding authors.
The above two projects were supported by the National Science & Technology Major Project of China, the CAMS Innovation Fund for Medical Sciences, the National Natural Science Foundation of China and the Medical Research Council, U.K., respectively.
The links of JMC publications are as below: