Synthesis and multilevel evaluation of benzimidazole-based anticancer compounds: DNA/serum albumin interaction, and in-depth theoretical insights
7 affiliations
- 1Institute of Health Sciences, Department of Basic Pharmaceutical Sciences, Suleyman Demirel University, Isparta, 32260, Türkiye, Turkey
- 2Faculty of Engineering and Natural Sciences, BahçeşehirUniversity, Istanbul, 34349, Türkiye, Turkey. [email protected]
- 3Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Suleyman Demirel University, Isparta, 32260, Türkiye, Turkey. [email protected]
- 4Faculty of Pharmacy, Department of Biochemistry, Suleyman Demirel University, 32260, Isparta, Turkey
- 5Health Specialties, Basic Sciences and Applications Unit, King Khalid University, Applied College, Mohayil Asir Abha, 61421, Saudi Arabia
- 6Department of Biology, Collage of Science, Princess Nourah bint Abdulrahman University, P.O.Box 84428, Riyadh, 11671, Saudi Arabia
- 7Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Suleyman Demirel University, Isparta, 32260, Türkiye, Turkey
Abstract
Within the scope of this investigation, two novel compounds ( 3a and 3b ) were designed and synthesized in two steps. Compounds 3a and 3b were tested utilizing the MTT study to evaluate their in vitro cytotoxic activity against healthy human embryonic kidney, lung cancer, breast cancer, and human liver cancer cell lines. It was determined that compound 3b exhibited high levels of cytotoxic activity against both liver and breast cancer cell lines, with IC 50 values of 10.83 and 11.55 µM, respectively. Also, to elucidate the anticancer mechanism of compounds, pro-apoptotic BAX and BiD , anti-apoptotic BCL2 and BCL-xl , oxidant enzymes PRDX1 and SOD1 levels were examined by RT-qPCR. Moreover, cellular oxidative stress levels were spectrophotometrically measured, and cellular senescence was evaluated via the senescence-associated β-galactosidase test. DFT calculations and RDG, ELF, and LOL analyses were performed to demonstrate the reactivity of these compounds. Compounds significantly down-regulated anti-apoptotic genes, whereas mRNA levels of pro-apoptotic genes were up-regulated in MCF-7 cells. Moreover, oxidative stress status was significantly increased depending on the compound treatment. Consistently, PRDX1 and SOD1 levels were also significantly up-regulated. Furthermore, cellular senescence was significantly induced by the compounds. Fluorescence spectroscopy demonstrated strong binding of both compounds with CT-DNA, characterized by static quenching mechanism and binding constants of 6.02 × 10 6 M − 1 (for 3a ) and 8.69 × 10 6 M − 1 (for 3b ), suggesting an intercalative binding mode. In contrast, moderate affinity toward BSA indicated suitable transport characteristics with reduced nonspecific protein binding. Molecular docking studies supported the experimental findings. These combined results verify the potential of the synthesized derivatives as promising candidates for further investigation as biologically active anticancer agents.
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BibTeX
@article{kundu2026synthesis,
title = {{Synthesis and multilevel evaluation of benzimidazole-based anticancer compounds: DNA/serum albumin interaction, and in-depth theoretical insights}},
author = {Sevgi Kundu and Senem Akkoç and Yalçın Erzurumlu and Sadeq K. Alhag and Lamya Ahmed Al‐Keridis and Mehran Feizi‐Dehnayebi},
journal = {Molecular and Cellular Biochemistry},
year = {2026},
month = jun,
doi = {10.1007/s11010-026-05600-3},
url = {https://doi.org/10.1007/s11010-026-05600-3},
note = {CC BY},
}
RIS
TY - JOUR
TI - Synthesis and multilevel evaluation of benzimidazole-based anticancer compounds: DNA/serum albumin interaction, and in-depth theoretical insights
AU - Sevgi Kundu
AU - Senem Akkoç
AU - Yalçın Erzurumlu
AU - Sadeq K. Alhag
AU - Lamya Ahmed Al‐Keridis
AU - Mehran Feizi‐Dehnayebi
PY - 2026
DA - 2026/06/23
JO - Molecular and Cellular Biochemistry
DO - 10.1007/s11010-026-05600-3
UR - https://doi.org/10.1007/s11010-026-05600-3
AB - Within the scope of this investigation, two novel compounds ( 3a and 3b ) were designed and synthesized in two steps. Compounds 3a and 3b were tested utilizing the MTT study to evaluate their in vitro cytotoxic activity against healthy human embryonic kidney, lung cancer, breast cancer, and human liver cancer cell lines. It was determined that compound 3b exhibited high levels of cytotoxic activity against both liver and breast cancer cell lines, with IC 50 values of 10.83 and 11.55 µM, respectively. Also, to elucidate the anticancer mechanism of compounds, pro-apoptotic BAX and BiD , anti-apoptotic BCL2 and BCL-xl , oxidant enzymes PRDX1 and SOD1 levels were examined by RT-qPCR. Moreover, cellular oxidative stress levels were spectrophotometrically measured, and cellular senescence was evaluated via the senescence-associated β-galactosidase test. DFT calculations and RDG, ELF, and LOL analyses were performed to demonstrate the reactivity of these compounds. Compounds significantly down-regulated anti-apoptotic genes, whereas mRNA levels of pro-apoptotic genes were up-regulated in MCF-7 cells. Moreover, oxidative stress status was significantly increased depending on the compound treatment. Consistently, PRDX1 and SOD1 levels were also significantly up-regulated. Furthermore, cellular senescence was significantly induced by the compounds. Fluorescence spectroscopy demonstrated strong binding of both compounds with CT-DNA, characterized by static quenching mechanism and binding constants of 6.02 × 10 6 M − 1 (for 3a ) and 8.69 × 10 6 M − 1 (for 3b ), suggesting an intercalative binding mode. In contrast, moderate affinity toward BSA indicated suitable transport characteristics with reduced nonspecific protein binding. Molecular docking studies supported the experimental findings. These combined results verify the potential of the synthesized derivatives as promising candidates for further investigation as biologically active anticancer agents.
SN - 0300-8177
SN - 1573-4919
ER -