Design, synthesis and molecular docking studies of novel benzimidazole-1,3,4-oxadiazole hybrids for their carbonic anhydrase inhibitory and antioxidant effects
Date
08.08.2022Author
Küçükoğlu, KaanÇevik, Ulviye Acar
Nadaroğlu, Hayrunnisa
Çelik, İsmail
Işık, Ayşen
Bostancı, Hayrani Eren
Özkay, Yusuf
Kaplancıklı, Zafer Asım
Metadata
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Kaan Küçükoğlu1 ● Ulviye Acar Çevik2 ● Hayrunnisa Nadaroglu3 ● Ismail Celik4 ● Ayşen Işık5 ● Hayrani Eren Bostancı 6 ● Yusuf Özkay2 ● Zafer Asım Kaplancıklı 2 Received: 7 April 2022 / Accepted: 28 July 2022 / Published online: 8 August 2022 © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022Abstract
In this study, eleven new compounds with a series of benzimidazole-1,3,4-oxadiazole derivatives structures were
synthesized and evaluated for their human (h) carbonic anhydrase inhibitory activities against two isoforms hCA I, hCA II,
and antioxidant activity. The synthesized compounds were fully characterized by spectral analysis methods such as
HNMR,
13
= 2.26 µM) for hCA I, the most potent compound 4a was
with the IC
C-NMR, and HRMS. Compared to acetazolamide (IC
50
50
= 1.989 µM) than
that of acetazolamide in these series. Among all the compounds, 4a (1.826 µM), 4d (1.502 µM), and 4g (1.886 µM) are the
most active hybrids against carbonic hCA II. Considering that compound 4a containing 4-bromophenyl structure is effective
on both hCA I and hCA II, it can be considered as a promising structure for the development of effective candidates with
potent CA inhibitory activities. TAS assay was used to evaluate the antioxidant activities of synthesized compounds. The
synthesized compound was analyzed for their in vitro cytotoxic activity on the L929 cell line by using MTT assay. In the last
step of this study, molecular docking studies were performed in order to compare the biological activities of the most active
molecules against the enzymes of hCAI and hCA II.
value of 1.322 µM and compound 4d is the other molecule with a greater IC
50
value (IC
50
1