Benzofuro[3,2-f][1]benzopyrans: a new class of antitubercular agents.
Alkylation of 2-hydroxydibenzofuran with 3-chloro-3-methyl-1-butyne, followed by Claisen rearrangement, gave access to 3,3-dimethyl-3Hbenzofuro[3,2-f][1]-benzopyran. Several derivatives modified at the pyran 1,2-double bond were prepared, including the corresponding dihydro compound and (+/-)-cis-diol, which was converted into diacetate and cyclic carbonate upon acylation. Both 3,3-dimethyl-3Hbenzofuro[3,2-f][1]benzopyran and 1,2-dihydro-3,3-dimethyl-3Hbenzofuro[3,2-f][1]benzopyran displayed significant activities when tested against Mycobacterium tuberculosis H37Rv and Beijing strains, with MIC99 in the range of 1-10 microg/ml. Further biological studies demonstrated good activities against drug-resistant mycobacterial strains. These compounds appear as promising specific antitubercular agents, since they exhibited neither significant cytotoxicity against mammal cells, nor effect on the growth of various bacteria and fungi.
Prado
Soizic
S
Laboratoire de Pharmacognosie, UMR/CNRS 8638, 4 avenue de l'Observatoire, 75006 Paris, France.
Ledeit
Hervé
H
Michel
Sylvie
S
Koch
Michel
M
Darbord
Jacques Christian
JC
Cole
Stewart T
ST
Tillequin
François
F
Brodin
Priscille
P
D039903:Actinobacteria / Q000187:drug effects; D000995:Antitubercular Agents / Q000737:chemistry / Q000145:classification* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D020102:Mycobacterium smegmatis / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects*
D000995:Antitubercular Agents