This study aimed to synthesize a novel series of N-heterocyclic compounds and evaluate their integrated pharmacological potential by coupling in vitro selective cytotoxicity on tumor and normal cell lines with predictive in silico ADME-Tox profiling. This research highlights the anti-cancer potential of twelve synthesized compounds, five of which are new chemical entities never before described in the literature. Their detailed structural characterization (NMR ¹H, ¹³C, IR), combined with in silico predictions (ADME-Tox), confirmed their ability to cross essential biological barriers, in particular the intestinal membrane and, for certain derivatives, the BBB. Biological evaluations conducted on SH-SY5Y (neuroblastoma) and HCT116 (colorectal carcinoma) cell lines revealed several compounds with IC₅₀ values lower than those of cisplatin while exhibiting reduced cytotoxicity towards the normal human epithelial BEAS-2B cell line. In particular, the compound (1H-imidazol-1-yl)methanol (designated as Compound 6 ) stands out with IC₅₀ values of 6.97 ± 0.06 µM on SH-SY5Y and 10.70 ± 0.33 µM on HCT116, significantly lower than those of cisplatin under the same experimental conditions. This profile, combined with virtually no toxicity on normal BEAS-2B cells (IC₅₀ > 800 µM), highlights its remarkable selectivity. These results highlight optimized pharmacological properties and suggest the potential for developing selective therapeutic agents against different types of cancer, particularly neuronal and colorectal tumors. Future research will focus on in-depth mechanistic studies and in vivo validation to optimize the efficacy, pharmacokinetics, and safety of these promising molecules.

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 µM, 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 µM. 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.

Sarı kantaron (Hypericum perforatum), geleneksel tıpta yaygın olarak kullanılan ve antimikrobiyal ile antitümör gibi önemli farmakolojik özellikler sergileyen bir bitkidir. Bu çalışmada, Malatya ili Pütürge ilçesi Kubbe Dağı eteklerinden toplanan sarı kantaron bitkisinden maserasyon yöntemiyle ekstre hazırlanmış, antimikrobiyal ve antikanser aktiviteleri açısından değerlendirilmiştir. Disk Difüzyon Testi kullanılarak Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 29213), Pseudomonas aeruginosa (ATCC 27853), Candida albicans (SC5314/ATCC MYA-2876) ve Candida glabrata (ATCC 2001) gibi mikroorganizmalar üzerindeki antimikrobiyal etkinliği araştırılmıştır. Antikanser aktivitek, MTT testiyle HCT116 (insan kolon kanseri), SH-SY5Y (insan beyin kanseri) ve BEAS-2B (insan sağlıklı akciğer hücresi) hücre hatlarında değerlendirilmiş ve elde edilen IC50 değerleri, standart antikanser ilacı Cisplatin ile karşılaştırılmıştır. Antimikrobiyal aktivite için, inhibisyon bölgeleri incelendiğinde C. albicans ve C. glabrata mayalarında inhibisyon göstermemiş, E. coli’de 9,33±0,78 mm, P. aeruginosa’da 12.17±0,53 mm ve S. aureus’ta 11.73±0.41 mm olarak hesaplanmıştır. Antkanser aktiviteleri ise sağlıklı hücre hattı BEAS-2B hücrelerinde 48.87±7.03 μg/mL, IC50 değeriyle düşük sitotoksisite, kanserli hücre hatlarında IC50 değerleri SH-SY5Y hücre hattında 23.27±3.35 μg/mL, HCT116 hücre hattında ise 10.67±3.05 μg/mL değerleriyle yüksek sitotoksisiste tespit edilmiştir. Sarı kantaron ekstresi sağlıklı hücrelere zarar vermeden kanser hücrelerini etkili bir şekilde hedef alabildiğini ve seçici toksisiteye sahip olabileceğini göstermektedir. Sonuç olarak; P. aeruginosa ve S. aureus’a karşı etkili antimikrobiyal aktivite ve kanserli hücre hatlarında güçlü sitotoksisite sergileyerek doğal tedavi ajanı olarak değerlendirilebilecek bir potansiyel ortaya koymuştur.