Our previous investigation revealed that some isothiazolo[5,4-b]pyridines substituted differently into isothiazole ring exhibited significant antimycobacterial effect under preliminary screening [1]. To study the above observation in more depth and to widen our knowledge of the structure-activity relationship (SAR), several classes of new related compounds were prepared and evaluated microbiologically.

Initially new isothiazolopyridines were screened against Mycobacterium tuberculosis H37Rv strain. The most active compound 9 was less active than reference drug (Rifampicin) and showed an inhibition activity of 100% at a concentration of 6.25 mg/mL. At the same time its 3-O-substituted isomer was completely inactive under preliminary screening. Compound 9 was also tested in VERO cells for determination cytotoxicity (IC₅₀) and the selectivity index (SI), defined as the IC₅₀/MIC. Unfortunately, compound 9 exhibited significant cytotoxic activity values of 4.1 µg/mL and low selectivity index (SI=0.68). The new prepared isothiazolopyridines were also evaluated against Mycobacterium fortuitum PMC 672 and Propionibacterium acnes PCM 2400. Only Mannich base 13d significantly reduced growth of M. fortuitum and this effect was observed for concentration below 1 mg/mL, similar as for the reference drug (Isoniazid). Isothiazolopyridine 13d was also active at MIC₉₀ > 1 mg/mL level. The results of an initial in vitro microbiological evaluation against Propionibacterium acnes appeared that only compound 6j showed strong activity (MIC₉₀ > 1 mg/mL) and demonstrated better activity at the concentration range of 1- 0.25 mg/mL when compared of that to the reference drug (Erythromycin).

[1]  Malinka W., Sieklucka-Dziuba M., Rajtar G., Zgodziński W., Kleinrok Z., Pharmazie  2000, 55, 416.

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/26752 must be provided.

1. Effect of the new derivatives of oxicams on efflux pumps overexpressed in resistant human colorectal adenocarcinoma cell line
2. Synthesis of new piroxicam derivatives and their influence on lipid bilayers
3. The interaction of new Piroxicam analogues with lipid bilayers – a calorimetric and fluorescence spectroscopic study
4. New Mannich bases of N-substituted 1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diones and their biological properties
5. The interaction of new fluphenazine analogues with lipid membrane
6. Synthesis of N-substituted benzo-1,2-thiazine 1,1-dioxide derivatives with potential anti-inflammatory activity
7. The influence of fluphenazine and its newly synthesized derivatives on the properties of liposomal membranes
8. The immunochemical studies of the glycinated glycoconjugates based on synthetic thioglycosides as mimic factors of bacterial endotoxins using in the polysaccharide vaccines preparation
9. Cellular senescence as a new approach in anti-cancer therapy
10. PYRIDO-1,2-THIAZINES AND THEIR IN VITRO ANITBACTERIAL EVALUATION
11. A STRUCTURAL AND SAR STUDY OF 2-[4-(SUBSTITUTED-PHENYL)PIPERAZIN-1-YLMETHYL]ISOTHIAZOLO[5,4-b]PYRIDINES WITH ANALGESIC ACTIVITY.