Anti-multidrug-resistant Gram-negative bacteria candidate drug was discovered by scientists

[ Science and Technology News of China Pharmaceutical Network ] Scientists have discovered drug candidates for anti-multidrug-resistant Gram-negative bacteria. The research has been funded by the National Natural Science Foundation of China and the Shanghai Pharmaceutical Institute. The research work was mainly carried out by Yang Liangshe, a researcher at the Shanghai Institute of Materia Medica, and Wang Haidong, a professor at Jiaxing College. They were completed by Tan Liang and Tao Junliang (co-cultivation).


Compound 12c antibacterial activity


Bacterial resistance, especially the resistance of Gram-negative bacteria, has become a major threat to human health. At present, there is a serious lack of safe and effective drugs for the treatment of multi-drug resistant Gram-negative bacteria, which is globally There are very few drug candidates for clinical research. In 2017, WHO divided the three categories into extremely important, important and medium-important categories based on the urgent need for new antibiotics. Listed as extremely important, including carbapenem-resistant Acinetobacter baumannii (CRA), Pseudomonas aeruginosa and extended-spectrum β-lactamase (ESBLS) Enterobacteriaceae (CRE) three bacteria, It is a multidrug resistant Gram-negative bacterium. Therefore, the development of broad-spectrum, potent anti-multidrug-resistant Gram-negative bacteria is a very urgent clinical demand.

The development of highly effective anti-multidrug-resistant Gram-negative bacteria is a world problem, because the resistance mechanism of negative bacteria is far more complicated than that of positive bacteria. The decrease of the outer membrane permeability of Gram-negative bacteria is an important reason for its multidrug resistance and pan-drug resistance. The principle of using iron from the bacterial iron carrier to skillfully combine antibiotics with iron carriers is to overcome the problem. An effective strategy for the barrier of outer membrane permeability of gram-negative bacteria. The research team of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Yang Yushe, used the clinical phase I BAL30072 as the lead compound. Through the structural optimization strategy, a series of iron carrier-monocyclic β-lactam conjugated compounds were designed and synthesized through in-depth structure-activity relationship and formation. In relational studies, candidate compound 12c was found (Fig., YT-14). YT-14 multidrug-resistant Acinetobacter baumannii (OXA23), Klebsiella pneumoniae (KPC-2), Pseudomonas aeruginosa (IMP4), and extended-spectrum β-lactamase (ESBLS) large intestine Both bacilli have strong inhibitory activity. In a mouse model of multidrug-resistant K. pneumoniae (KPC-2) infection, YT-14 has a stronger protective effect on mice than BAL30072 and meropenem. In conclusion, YT-14 has potent, broad-spectrum anti-multidrug-resistant Gram-negative bacteria activity and excellent metabolic properties. It is a promising candidate compound against Gram-negative bacteria and deserves further research and development.

The research was published online March 13 in the Journal of Medicinal Chemistry, the journal of the American Chemical Society. The research work was mainly carried out by Yang Liangshe, a researcher at the Shanghai Institute of Materia Medica, and Wang Haidong, a professor at Jiaxing College. They were completed by Tan Liang and Tao Junliang (co-cultivation).

The study was funded by the National Natural Science Foundation of China and the Shanghai Institute of Drugs.

Active Pharmaceutical Ingredient

medicinal extract,Pure loofah powder,blackberry juice powder

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