Biological activity and computational analysis of novel acrylonitrile derived benzazoles as potent antiproliferative agents for pancreatic adenocarcinoma with antioxidative properties

Beč, Anja; Persoons, Leentje; Daelemans, Dirk; Starčević, Kristina; Vianello, Robert; Hranjec, Marijana (2024) Biological activity and computational analysis of novel acrylonitrile derived benzazoles as potent antiproliferative agents for pancreatic adenocarcinoma with antioxidative properties. Bioorganic Chemistry, 147 . ISSN 0045-2068

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Abstract

Continuing our research into the anticancer properties of acrylonitriles, we present a study involving the design, synthesis, computational analysis, and biological assessment of novel acrylonitriles derived from methoxy, hydroxy, and N-substituted benzazole. Our aim was to examine how varying the number of methoxy and hydroxy groups, as well as the N-substituents on the benzimidazole core, influences their biological activity. The newly synthesized acrylonitriles exhibited strong and selective antiproliferative effects against the Capan-1 pancreatic adenocarcinoma cell line, with IC50 values ranging from 1.2 to 5.3 μM. Consequently, these compounds were further evaluated in three other pancreatic adenocarcinoma cell lines, while their impact on normal PBMC cells was also investigated to determine selectivity. Among these compounds, the monohydroxy-substituted benzimidazole derivative 27 emerged with the most profound and broad-spectrum anticancer antiproliferative activity being emerged as a promising lead candidate. Moreover, a majority of the acrylonitriles in this series exhibited significant antioxidative activity, surpassing that of the reference molecule BHT, as demonstrated by the FRAP assay (ranging from 3200 to 5235 mmolFe2+/mmolC). Computational analysis highlighted the prevalence of electron ionization in conferring antioxidant properties, with computed ionization energies correlating well with observed activities.

Item Type:	Article
Uncontrolled Keywords:	acrylonitriles; antioxidant activity; antiproliferative activity; benzimidazoles; benzothiazoles; pancreatic cancer
Subjects:	NATURAL SCIENCES NATURAL SCIENCES > Chemistry NATURAL SCIENCES > Chemistry > Physical Chemistry NATURAL SCIENCES > Chemistry > Organic Chemistry
Divisions:	Division of Organic Chemistry and Biochemistry
Projects:	Project title Project leader Project code Project type Istraživanje antioksidativnog djelovanja benzazolskog skeleta u dizajnu novih antitumorskih agensa-AntioxPot Marijana Hranjec IP-2018-01-4379 HRZZ Dizajn, sinteza i računalna analiza novih optičkih kemijskih pH osjetilnih derivata benzazola-BenzpHSens Robert Vianello IP-2020-02-8090 HRZZ
Depositing User:	Robert Vianello
Date Deposited:	13 Jan 2026 10:08
URI:	http://fulir.irb.hr/id/eprint/10826
DOI:	10.1016/j.bioorg.2024.107326

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