TY - JOUR

T1 - Diverse Biological Activity of Benzofuroxan/Sterically Hindered Phenols Hybrids

AU - Chugunova, Elena

AU - Gibadullina, Elmira

AU - Matylitsky, Kirill

AU - Bazarbayev, Baurat

AU - Neganova, Margarita

AU - Volcho, Konstantin

AU - Rogachev, Artem

AU - Akylbekov, Nurgali

AU - Nguyen, Hoang Bao Tran

AU - Voloshina, Alexandra

AU - Lyubina, Anna

AU - Amerhanova, Syumbelya

AU - Syakaev, Victor

AU - Burilov, Alexander

AU - Appazov, Nurbol

AU - Zhanakov, Mukhtar

AU - Kuhn, Leah

AU - Sinyashin, Oleg

AU - Alabugin, Igor

N1 - Funding: The synthesis, the study of anticancer and antimicrobial activities were carried out at the Arbuzov Institute of Organic and Physical Chemistry and were supported by the Ministry of Science and Higher Education of the Russian Federation at FRC Kazan Scientific Center (grant No. 075-15-2022-1128). Two-dimensional NMR experiments were funded by the government assignment for the FRC Kazan Scientific Center of RAS. The study of hemolytic activity was funded by the financial support for research from the Ministry of Agriculture of the Republic of Kazakhstan (BR10764960). L.K. acknowledges support by the National Science Foundation Graduate Research Fellowship under Grant No. 1449440 for quantum-chemical computations realization.

PY - 2023/3/28

Y1 - 2023/3/28

N2 - Combining two pharmacophores in a molecule can lead to useful synergistic effects. Herein, we show hybrid systems that combine sterically hindered phenols with dinitrobenzofuroxan fragments exhibit a broad range of biological activities. The modular assembly of such phenol/benzofuroxan hybrids allows variations in the phenol/benzofuroxan ratio. Interestingly, the antimicrobial activity only appears when at least two benzofuroxan moieties are introduced per phenol. The most potent of the synthesized compounds exhibit high cytotoxicity against human duodenal adenocarcinoma (HuTu 80), human breast adenocarcinoma (MCF-7), and human cervical carcinoma cell lines. This toxicity is associated with the induction of apoptosis via the internal mitochondrial pathway and an increase in ROS production. Encouragingly, the index of selectivity relative to healthy tissues exceeds that for the reference drugs Doxorubicin and Sorafenib. The biostability of the leading compounds in whole mice blood is sufficiently high for their future quantification in biological matrices.

AB - Combining two pharmacophores in a molecule can lead to useful synergistic effects. Herein, we show hybrid systems that combine sterically hindered phenols with dinitrobenzofuroxan fragments exhibit a broad range of biological activities. The modular assembly of such phenol/benzofuroxan hybrids allows variations in the phenol/benzofuroxan ratio. Interestingly, the antimicrobial activity only appears when at least two benzofuroxan moieties are introduced per phenol. The most potent of the synthesized compounds exhibit high cytotoxicity against human duodenal adenocarcinoma (HuTu 80), human breast adenocarcinoma (MCF-7), and human cervical carcinoma cell lines. This toxicity is associated with the induction of apoptosis via the internal mitochondrial pathway and an increase in ROS production. Encouragingly, the index of selectivity relative to healthy tissues exceeds that for the reference drugs Doxorubicin and Sorafenib. The biostability of the leading compounds in whole mice blood is sufficiently high for their future quantification in biological matrices.

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85154575178&origin=inward&txGid=394b7b2fea62d87018d1c885f8e744e8

U2 - 10.3390/ph16040499

DO - 10.3390/ph16040499

M3 - Article

C2 - 37111256

VL - 16

JO - Pharmaceuticals

JF - Pharmaceuticals

SN - 1424-8247

IS - 4

M1 - 499

ER -