Benzimidazole-hydrazone derivatives: Synthesis, in vitro anticancer, antimicrobial, antioxidant activities, in silico DFT and ADMET studies
Date
14.08.2022Author
Işık, AyşenÇevik, Ulviye Acar
Çelik, İsmail
Bostancı, Hayrani Eren
Karayel, Arzu
Gündoğdu, Gülsüm
İnce, Ufuk
Koçak, Ahmet
Özkay, Yusuf
Kaplancıklı, Zafer Asım
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Ays¸ en IS¸ IKa , Ulviye Acar Çevik b,∗ , Ismail Çelikc , Hayrani Eren Bostancı d, Arzu Karayel e , Gülsüm Gündogdu ˘ f , Ufuk Ince g , Ahmet Koçak h, Yusuf Özkay b , Zafer Asım Kaplancıklı b a Department of Biochemistry, Faculty of Science, Selçuk University, Konya, Turkey b Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskis¸ ehir 26470, Turkey c Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Erciyes University, Kayseri 38039, Turkey d Department of Biochemistry, Faculty of Pharmacy, Cumhuriyet University, Sivas, Turkey e Department of Physics, Faculty of Arts and Science, Hitit University, Çorum 19030, Turkey f Department of Energy Science and Technology, Faculty of Science, Turkish-German University, Istanbul 34820, Turkey g Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Erciyes University, Kayseri 38039, Turkey h Department of Chemistry, Faculty of Science, Selçuk University, Konya, TurkeyAbstract
Based on the biologically active heterocycle compounds, a series of new benzimidazole-hydrazone deriva-
tives ( 3a-3j ) were synthesized, starting from 4-(6-chloro-1 H -benzimidazol-2-yl) benzohydrazide. The syn-
thesized compounds were characterized by
1
H NMR,
13
C NMR, and HRMS spectroscopic methods. The
synthesized compounds were preliminarily evaluated for their in vitro antimicrobial, anticancer and an-
tioxidant activity. The antimicrobial activity was checked against S. aureus ATCC 29213, E. coli ATCC 25922,
and C. albicans ATCC 10231 by micro-dilution method. The findings exhibited that the compounds pos-
sessed moderate antimicrobial potential. The compounds were also checked for their in vitro anticancer
activities against HT-29 (colorectal cancer cell line) using the MTT assay. It was observed that all the
compounds 3a-3j showed weak antiproliferative activity against HT-29 cells. The compounds were also
analyzed for their antioxidant capacity by Tas & Tos activity. The compound 3d showed a high anti-
oxidative effect with 30.81 μmol H
O
2
2
Equiv./L value. The lowest energy state of compound 3d was real-
ized in DMSO medium by using the B3LYP method at 6–311G (d,p) level, the optimized geometry of it is
about 0.50 and 17 kcal/ mol more stable than in other solvents and the gas phase, respectively. The lower
E = 3.563 eV indicates the higher reactivity of compound 3d , this is compatible with biological experi-
mental data and shows high antioxidant property of the compound. In silico ADMET studies of compound
3d were performed. Indexing of the X-ray powder diffraction pattern was performed for compound 3a .