Synthesis, characterization, and anticancer potential of novel NHC ligands and their selenium complexes - A combined in vitro and in silico investigation

Sep 28, 2026

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Efficiently synthesized new benzimidazolium salts (A1–A6) and their selenium-NHC complexes (B1–B6) were evaluated for cytotoxicity against HCT116 and SH-SY5Y cancer cell lines and BEAS-2B normal cells. Benzimidazolium salts showed substantially higher cytotoxicity than selenium derivatives, with A3–A5 displaying the strongest effects and IC50 values (3.09–26.12 mM) about ten times lower than cisplatin. Structure–activity analysis identified the benzimidazolium core as the pharmacophore and bulky aromatic substitutions as key enhancers, while selenium incorporation markedly reduced or eliminated cytotoxicity up to 800 mM. Molecular docking against PARP-1 and tubulin supported the inhibitory potential of A3–A5.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

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Introduction

Background and motivation

Selenium-based NHC rationale

RSC Advances PAPER Cite this: RSC Adv., 2026, 16, 409 Received 31st October 2025 Accepted 12th December 2025 DOI: 10.1039/d5ra08393a [rsc.li/rsc-advances](rsc.li/rsc-advances) Synthesis, characterization, and anticancer potential of novel NHC ligands and their selenium complexes: a combined in vitro and in silico investigation Boutheina Boualia,ab Abd el-Krim Sandeli, c Enes Evren, b I˙smail ¨Ozdemir, bd Hüseyin Karci, b Muhammed Dündar, e I˙lknur ¨Ozdemir, bd Nevin Gürbüz, bd Ahmet Koç f and Houssem Boulebd *g We report herein the eﬃcient synthesis of new benzimidazolium salts (A1–A6) and their corresponding selenium-NHC complexes (B1–B6), along with the evaluation of their cytotoxicity proﬁles against two cancer cell lines (HCT116 and SH-SY5Y) and one normal cell line (BEAS-2B) . The ﬁndings revealed that the benzimidazolium salts (A1–A6) exhibited signiﬁcantly higher cytotoxicity toward all tested cell lines compared to their selenium derivatives (B1–B6) . Among them, compounds A3, A4, and A5 showed the most potent cytotoxic eﬀects, with IC50 values ranging from 3 . 09 to 26 .12 mM, approximately ten times lower than that of cisplatin. However, these compounds also exhibited relatively low IC50 values in normal BEAS-2B cells, although still higher than those observed in the cancer cell lines, indicating a preferential cytotoxicity toward cancer cells. Structure–activity relationship analysis revealed that the benzimidazolium core acts as the pharmacophore of these compounds, while substitution on the aromatic ring—particularly with bulky groups—enhances cytotoxicity. Conversely, incorporation of the selenium atom was found to markedly reduce or even eliminate cytotoxicity up to concentrations of 800 mM. Further in silico studies were conducted to gain a deeper understanding of the molecular structures and chemical reactivity of these compounds. In addition, molecular docking studies against PARP-1 and tubulin highlighted the strong inhibitory potential of the most active compounds (A3, A4, and A5) toward both targets, suggesting their potential involvement in the observed cytotoxic eﬀects. Overall, these investigations propose benzimidazolium salts A3, A4, and A5 as promising anticancer agents and highlight the selenium derivatives as non-toxic selenium-based NHC complexes. Further studies should be undertaken to optimize the biological activity of these compounds and to enhance their selectivity toward cancer cells. 1. Introduction Cancer remains a leading cause of morbidity and mortality worldwide, necessitating the continued development of novel a The Molecular and Structural Environmental Chemistry Research Unit, Faculty of Exact Sciences, Brother's Mentouri Constantine 1 University, Constantine, Algeria b˙Inönü University Drug Administration and Research Center, 44280-Malatya, Turkey cPharmaceutical Sciences Research Center (CRSP), Constantine 25000, Algeria d˙Inönü University, Faculty of Arts and Sciences, Department of Chemistry, 44280-Malatya, Turkey eInönü University, Faculty of Arts and Sciences, Department of Molecular Biology and Genetics, 44280-Malatya, Turkey f˙Inönü University, Faculty of Medicine, Department of Medical Genetics, 44280-Malatya, Turkey gLaboratory of Synthesis of Molecules with Biological Interest, Frres Mentouri Constantine 1 University, Constantine 25017, Algeria. E-mail: boulebd.houssem@ [umc.edu.dz](umc.edu.dz) therapeutic agents with improved eﬃcacy and selectivity. The identi􀀁cation of cisplatin's anticancer properties by Rosenberg1 led to metal-based compounds becoming a major focus in anticancer drug development. Since then, the search for novel metal-based therapeutics has intensi􀀁ed. However, despite their success, platinum-based drugs such as cisplatin suﬀer from severe side eﬀects, limited selectivity toward malignant cells, and the emergence of resistance.2 These challenges have stimulated extensive eﬀorts to design and evaluate new classes of i

FAQs

What compounds were synthesized and compared in the study?

The study synthesized benzimidazolium salts (A1–A6) and their corresponding selenium-NHC complexes (B1–B6). Cytotoxicity was then evaluated for both groups.

Which cell lines were used to test cytotoxicity?

Cytotoxicity was measured against two cancer cell lines (HCT116 and SH-SY5Y) and one normal cell line (BEAS-2B).

How did selenium incorporation affect cytotoxicity and target inhibition?

Selenium incorporation markedly reduced or eliminated cytotoxicity up to concentrations of 800 mM. Docking studies against PARP-1 and tubulin indicated strong inhibitory potential for the most active salts (A3, A4, A5).

Sep 28, 2026

Uploaded by Grenda