Akademik Veri Yönetim Sistemi
VII. Farmasötik Kimya Kongresi, İzmir, Türkiye, 26 - 28 Ekim 2024
Among
the several forms of NSAIDs, imidazole and fused imidazole with six-membered
rings hold a prominent role as analgesic and anti-inflammatory medicines. The
benzimidazole moiety meets the minimum structural requirements for
anti-inflammatory drugs. It has been reported that many molecules containing
benzimidazole moiety have significant anti-inflammatory as well as analgesic
activity [1]. The aim of this study to design, synthesize, characterize,
docking Studies and investigate the anti-inflammatory activity of new
benzimidazole derivatives C1-C5 (C1;
6-chloro-2-(2,5-difluorophenyl)-1-ethyl-5-fluoro-1H-benzo[d]imidazole, C2;
6-chloro-2-(2,4-dimethoxyphenyl)-5-fluoro-1H-benzo[d]imidazole, C3;
6-chloro-2-(3,4-dimethoxyphenyl)-5-fluoro-1H-benzo[d]imidazole, C4;
6-chloro-2-(2,6-dichlorophenyl)-5-fluoro-1H-benzo[d]imidazole, C5; 6-chloro-2-(2,4-dichlorophenyl)-5-fluoro-1H-benzo[d]imidazole)
5-chloro-4-fluoro-2-nitroaniline was dissolved in
ethanol and reduced with SnCl2/HCl to give
4-chloro-5-fluorobenzene-1,2-diamine [2]. 1 mmol of sodium metabisulphite salt
of the corresponding substituted benzaldehydes and 1 mmol of
4-chloro-5-fluorobenzene-1,2-diamine were refluxed in DMF at 135 0C
for 12 hours. The end of the reaction was checked by TLC and the reaction was
terminated. The reaction medium was cooled and poured into cold water [3]. The
precipitate was filtered and dried and purified by column chromatography to
obtained pure compounds C1-C5. The chemical structures of the final C1-C5
compounds were determined using various spectral methods (MS, 1H NMR
and 13C NMR). The synthesized compounds were tested for
anti-inflammatory activity using Human Red Blood Cell Membrane Stabilization
Capacity. Docking study was performed against COX-2 enzyme using Cresset Flare
software and the corresponding scores were recorded.
The highest activity in stabilisation capacity of
human red blood cell membranes was found in C1 and C3 with 51.74
± 2.63% and 36.88 ± 0.44% stabilisation capacity, respectively, compared to the
standard anti-inflammatory drug indomethacin, which showed 27.38 ± 1.48%
inhibition. The docking study against the COX-2 (PDB; 5IKQ) enzyme showed that
all synthesized compounds showed a lower energy score (C1=-8.60, C2=-8.29,
C3=-8.80, C4=-9.52, C5=-9,60) than indomethacin (-7,98
kcal/mol). This indicates a more stable binding interaction of compounds C1-C5
when bound to the COX-2 enzyme.
The compounds C1-C5
could be good drug candidates with anti-inflammatory properties and can be used
as lead compounds for discovery a new anti-inflammatory drug.