Circular dichroism and anomeric configuration assignment of benzimidazole C-nucleoside analogs

Sallam, Mohammed A.E.; Hamid, Omnia G. Abdel; Gossen, Verena; Raabe, Gerhard; Aboul‐Ela, Salah

doi:10.1016/j.carres.2012.07.008

Cited by 3 publications

(1 citation statement)

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“…[ 37,38 ] Direct acid‐catalyzed condensation reaction of different substituted o ‐phenylene diamines with different aldonates of l ‐arabinose, d ‐ribose, d ‐glucose, and d ‐gulose was also reported. [ 24,39 ] In this study, direct condensation of different o ‐phenylene diamines 3 with calcium d ‐galactonate 4 in the presence of concentrated hydrochloric and phosphoric acids at 160°C was established to afford the corresponding (1 S ,2 R ,3 S ,4 R )‐2‐(1,2,3,4,5‐pentahydroxy)pentyl‐1 H ‐benzimidazole derivatives 5–11 in good yield (84%–91%) (Scheme 1). Structural elucidation of the synthesized compounds was verified from their nuclear magnetic resonance (NMR) spectral analysis ( 1 H‐, 13 C‐NMR, 2D 1 H‐ 1 H COSY, and 1 H‐ 13 C HMQC).…”

Section: Resultsmentioning

confidence: 99%

Discovery of novel benzimidazole acyclic C‐nucleoside DNA intercalators halting breast cancer growth

Abd Al Moaty,

El Kilany,

Awad

et al. 2023

Archiv der Pharmazie

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Breast cancer continues to be the most frequent cancer worldwide. In practice, successful clinical outcomes were achieved via targeting DNA. Along with the advances in introducing new DNA‐targeting agents, the “sugar approach” design was employed herein to develop new intercalators bearing pharmacophoric motifs tethered to carbohydrate appendages. Accordingly, new benzimidazole acyclic C‐nucleosides were rationally designed, synthesized and assayed via MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide) assay to evaluate their cytotoxicity against MCF‐7 and MDA‐MB‐231 breast cancer cells compared to normal fibroblasts (Wi‐38), compared to doxorubicin. (1S,2R,3S,4R)‐2‐(1,2,3,4,5‐Pentahydroxy)pentyl‐1H‐5,6‐dichlorobenzimidazole 7 and (1S,2R,3S,4R)‐2‐(1,2,3,4,5‐pentahydroxy)pentyl‐1H‐naphthimidazole 13 were the most potent and selective derivatives against MCF‐7 (half‐maximal inhibitory concentration [IC50] = 0.060 and 0.080 µM, selectivity index [SI] = 9.68 and 8.27, respectively) and MDA‐MB‐231 cells (IC50 = 0.299 and 0.166 µM, SI = 1.94 and 3.98, respectively). Thus, they were identified as the study hits for mechanistic studies. Both derivatives induced DNA damage at 0.24 and 0.29 μM, respectively. The DNA damage kinetics were studied compared to doxorubicin, where they both induced faster damage than doxorubicin. This indicated that 7 and 13 showed a more potent DNA‐damaging effect than doxorubicin. Docking simulations within the DNA double strands highlighted the role of both the heterocyclic core and the sugar side chain in exhibiting key H‐bond interactions with DNA bases.

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Section: Resultsmentioning

confidence: 99%