Keeping
in view various pharmacological attributes of indole and coumarin
derivatives, a new series of indolindione–coumarin molecular
hybrids was rationally designed and synthesized. All synthesized hybrid
molecules were evaluated for their antimicrobial potential against
Gram-negative bacterial strains (
Escherichia coli
and
Salmonella enterica
), Gram-positive
bacterial strains (
Staphylococcus aureus
and
Mycobacterium smegmatis
), and
four fungal strains (
Candida albicans
,
Alternaria mali
,
Penicillium
sp., and
Fusarium oxysporum
) by using the agar gel diffusion method. Among all synthetics, compounds
K-1
and
K-2
were found to be the best antimicrobial
agents with the minimum inhibitory concentration values of 30 and
312 μg/mL, against
Penicillium
sp. and
S. aureus
, respectively.
The biological data revealed some interesting facts about the structure–activity
relationship which state that the electronic environment on the indolinedione
moiety and carbon chain length between indolinedione and triazole
moieties considerably affect the antimicrobial potential of the synthesized
hybrids. Various types of binding interactions of
K-2
within the active site of
S. aureus
dihydrofolate reductase were also streamlined by molecular modeling
studies, which revealed the possible mechanism for potent antibacterial
activity of the compound.
Keeping in view various
pharmacological attributes of curcumin, coumarin, and isatin derivatives,
triazole-tethered monocarbonyl curcumin–coumarin and curcumin–isatin
molecular hybrids have been synthesized and evaluated for their antibacterial
potential against Gram-positive (
Enterococcus faecalis
and
Staphylococcus aureus
) and Gram-negative
(
Pseudomonas aeruginosa
and
Escherichia coli
) human pathogenic bacterial strains.
Among all hybrid molecules,
A-4
and
B-38
showed the most potent antibacterial activity with inhibition zones
of 29 and 31 mm along with MIC values of 12.50 and 6.25 μg/mL,
respectively. Structure–activity relationship that emerged
from biological data revealed that the two-carbon alkyl chain between
triazole and coumarin/isatin moiety is well tolerable for the activity.
Bromo substitution at the fifth position of isatin, para-cholo substitution
in the case of curcumin–isatin, and para-methoxy in the case
of curcumin–coumarin hybrids on ring A of curcumin are most
suitable groups for the antibacterial activity. Various types of binding
interactions of
A-4
and
B-38
within the
active site of dihydrofolate reductase (DHFR) of
S.
aureus
are also streamlined by molecular modeling
studies, suggesting their capability in completely blocking DHFR.
A novel series of triazole-linked isatin-indole-3-carboxaldehyde hybrids based on the febuxostat skeleton and its binding site interactions were rationally designed and synthesized as potential xanthine oxidase inhibitors. Among the synthesized hybrids, A19 showed the most potent xanthine oxidase inhibition (IC 50 = 0.37 µM) with the mixed-type inhibitory scenario. Structure-activity relationship studies revealed that methoxy (OCH 3 ) substitution on position 5 of the isatin nucleus and a two-carbon distance between isatin and the triazole moiety is most tolerable for the inhibitory
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