Synthesis and biological activities of three-molecule conjugates with para-aminosalicylic acid as parent nucleus
10.16438/j.0513-4870.2022-0101
- VernacularTitle:以对氨基水杨酸为母核的三分子缀合物的合成及其生物活性研究
- Author:
Yan-hui REN
1
;
Li FAN
1
;
Jun-qi XU
2
;
Jian-ping XIE
2
;
Le-ping DAI
1
;
Dan MAO
1
;
Xi YANG
1
;
Da-cheng YANG
1
Author Information
1. Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China
2. College of Life Science, Southwest University, Chongqing 400715, China
- Publication Type:Research Article
- Keywords:
italic>p-aminosalicylic acid;
isonicotinic acid;
fluoroquinolone;
activity against Mycobacterium tuberculosis;
activity against human pathogenic bacteria
- From:
Acta Pharmaceutica Sinica
2022;57(7):2126-2138
- CountryChina
- Language:Chinese
-
Abstract:
Based on the idea of multi-target drug design, taking p-aminosalicylic acid (PAS) as the parent nucleus, the unreported target molecules TM1 and TM2 were designed with PAS, isonicotinic acid and fluoroquinolone as three structural units conjugated by different linkers. Sixteen target molecules were synthesized by multi-step reaction, and their activities against Mycobacterium tuberculosis and human pathogenic bacteria were evaluated. The results showed that the anti-tuberculosis activity of TM2a was stronger than those of the assayed fluoroquinolones, while TM1a was comparable to that of clinafloxacin, the most active compound of the positive control fluoroquinolones; TM1a showed the strongest inhibitory activity to all almost tested strains, TM1b and TM2a showed very strong inhibitory activity to most strains, and TM1h/2h had strong inhibitory activity to some strains; The inhibitory activities of TM1a/1h on Staphylococcus aureus ATCC14125 are much stronger than those of fluoroquinolones, which eminently deserves further study. The hemolysis test results showed that the highly active molecules TM1a and TM2a exhibited relative safety below the concentrations of 8 and 32 μg·mL-1, respectively. In this study, a new hybrid molecule of three molecular pharmacophores with PAS as the parent nucleus was synthesized for the first time, and some of which have highly strong antibacterial activity, which provides a new idea for the research and development of antibiotics.
