anti-Tuberculosis natural products: synthesis and biological evaluation of pyridoacridine alkaloids related to ascididemin |
| |
| Authors: | David R Appleton A Norrie Pearce Brent R Copp |
| |
| Institution: | 1. Centre for Natural Products Research and Drug Discovery, Department of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia;2. Department of Chemistry, The University of Auckland, Private Bag 92019, Auckland, New Zealand |
| |
| Abstract: | There is an urgent need for novel therapeutics possessing new modes of action to treat tuberculosis (TB) infections. In this study we report on the synthesis and biological evaluation of a series of pyrido2,3,4-kl]acridin-6-one alkaloids related to the anti-TB (MIC 0.35 μM) but cytotoxic (IC50 <0.14 μM) marine natural product ascididemin (1). The most interesting compounds identified were 21 and 24, which were found to inhibit the growth of Mycobacterium tuberculosis (Mtb) H37Rv with MIC 2.0 μM, but with negligible cytotoxicity towards Vero and P388 cells (IC50>25 μM). Another analogue (10) was evaluated against a range of singly-drug-resistant strains of Mtb and was found to exhibit no cross-resistance. These results suggest that the pyrido2,3,4-kl]acridin-6-one skeleton may provide a useful scaffold for future studies directed towards possible anti-TB drugs. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
