J. Med Dr. Chem: Kev Tshawb Fawb Thiab Kev Txhim Kho Ntawm Lub Tswv Yim Tshiab Los Tawm Tsam Tshuaj Tiv Thaiv Kab Mob Kab Mob

Tshuaj tiv thaiv kab mob sib kis tau dhau los ua kev kub ntxhov thoob ntiaj teb rau tib neeg kev noj qab haus huv. Ntawm 6 yam tshuaj tiv taus ESKEPA cov kab mob (Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Enterobacter, Pseudomonas aeruginosa, thiab Acinetobacter baumannii) uas xav tau sai los tsim cov tshuaj tshiab los ntawm WHO, plaub hom yog gram-negative bacteria, uas tuaj yeem ua rau cov kab mob sib kis tuag taus. Polymyxin yog cyclic lipopeptide los ntawm Bacillus. Nws yog lub chaw kho mob hu ua&"kab kawg ntawm kev tiv thaiv &" tiv thaiv cov tshuaj tiv thaiv kab mob gram-negative kab mob. Txawm li cas los xij, cov kev mob tshwm sim nephrotoxic ntawm polymyxin txwv nws Rau nws daim ntawv thov kev kho mob, kev txhim kho cov txiaj ntsig zoo tshiab thiab tsis muaj tshuaj lom los tiv thaiv kab mob-tsis zoo tshuaj tua kab mob tseem tab tom tshwm sim.

Pab pawg Huang Wei tshawb fawb ntawm Shanghai Institute of Materia Medica, Suav Academy ntawm Kev Tshawb Fawb thiab Lan Lefu cov pab pawg tshawb fawb tau koom tes thiab luam tawm lub npe" Tag Nrho thiab Semisyntheses ntawm Polymyxin Analogues nrog 2-Thr lossis 10-Thr Hloov Kho rau Decipher Tus Qauv -" pe J. Med. Chem. Kev Txheeb Ze Kev Txheeb Ze thiab Txhim Kho Kev Ua Haujlwm Antibacterial" tsab xov xwm, hauv kev pom ntawm cov qauv tsis meej-kev sib raug zoo ntawm polymyxin hauv 2-Thr thiab 10-Thr, txoj hauv kev los ntawm kev sib xyaw ua ke thiab ib nrab ua ke ua ke qhia kev sib raug zoo ntawm ob qhov chaw no. Cov qauv-kev sib raug zoo txuas ntxiv muab cov tswv yim tshiab thiab cov tswv yim rau kev txhim kho polymyxin.

Pab pawg tshawb fawb tau siv ob qhov kev sib xyaw ua ke tag nrho cov txheej txheem thiab xaiv cov txheej txheem ua kua ib nrab ua ke, hloov pauv rau polymyxin 2-Thr lossis 10-Thr, thiab sib sau ua ke ntawm polymyxin cov txiaj ntsig. Hauv qhov kev sim tshuaj tiv thaiv kab mob tiv thaiv kab mob kev ua haujlwm, kev hloov pauv hloov pauv ntawm cov txiaj ntsig tau pom tias hloov pauv ntawm 2-/10-Thr nrog cov amino acids nrog hydrophobic sab saw tuaj yeem ua haujlwm zoo tiv thaiv Pseudomonas aeruginosa; Cov khoom siv hloov pauv hloov pauv ntawm cov txiaj ntsig tau qhia tias cov amino acetyl esterification ntawm 2-/10-Thr muaj cov tshuaj tua kab mob zoo heev. Ntawm lawv, kev sib xyaw 76 yog 2-8 zaug ntau dua tiv thaiv kab mob sib txawv, thiab tseem muaj tshuaj lom rau HK-2 hlwb. Txo (Daim duab 1). Cov ntaub ntawv no tso lub hauv paus rau kev txhim kho ntxiv ntawm kev tshawb fawb tshuaj tua kab mob tshiab thiab txhim kho raws li kev hloov kho polymyxin