Chalcones and flavonoids as anti-tuberculosis agents.
A series of flavonoids, chalcones and chalcone-like compounds were evaluated for inhibitory activity against Mycobacterium tuberculosis H37Rv. Among them, eight compounds exhibited >90% inhibition on the growth of the bacteria at a concentration of 12.5 microg/mL. Chalcones 1-(2-hydroxyphenyl)-3-(3-chlorophenyl)-2-propen-1-one (22) and 1-(2-hydroxyphenyl)-3-(3-iodophenyl)-2-propen-1-one (37) demonstrated 90 and 92% inhibition, respectively. Chalcone-like compounds (heterocyclic ring-substituted 2-propen-1-one) 1-(4-fluorophenyl)-3-(pyridin-3-yl)-2-propen-1-one (48), 1-(3-hydroxyphenyl)-3-(phenanthren-9-yl)-2-propen-1-one (49), 1-(pyridin-3-yl)-3-(phenanthen-9-yl)-2-propen-1-one (50) and 1-(furan-2-yl)-3-phenyl-2-propen-1-one (51) exhibited 98, 97, 96 and 96% inhibition, respectively. The actual minimum inhibitory concentrations (MIC), defined as the lowest concentration inhibiting 99% of the inoculum, for 22, 37, 48, 49, 50 and 51 were 20.3, 31.5, 48.3, >35.7, 6.8 and 19.2, respectively. A hydrophobic substituent on one aromatic ring, and a hydrogen-bonding group on the other aromatic ring resulted in increased anti-TB activity of the chalcones and chalcone-like compounds. Flavones and flavanones are more geometrically constrained than the corresponding chalcone analogues. The decreased activity of the flavones with respect to the chalcones may be due to the confinement of the terminal aromatic rings to the same plane.
Lin
Yuh-Meei
YM
MediChem Life Sciences, 2501 Davey Road, Woodridge, IL 60517, USA.
Zhou
Yasheen
Y
Flavin
Michael T
MT
Zhou
Li-Ming
LM
Nie
Weiguo
W
Chen
Fa-Ching
FC
D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002599:Chalcone / Q000138:chemical synthesis* / Q000494:pharmacology; D005419:Flavonoids / Q000138:chemical synthesis* / Q000494:pharmacology; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013329:Structure-Activity Relationship
D000995:Antitubercular Agents; D005419:Flavonoids; D002599:Chalcone