Dual Diomarkers Triggered Prodrugs for Precise Treatment of Melanoma:Design, Synthesis and Activities

doi:10.1007/s40242-022-2121-y

Chemical Research in Chinese Universities ›› 2022, Vol. 38 ›› Issue (4): 949-956.doi: 10.1007/s40242-022-2121-y

• Articles • Previous Articles Next Articles

Dual Diomarkers Triggered Prodrugs for Precise Treatment of Melanoma:Design, Synthesis and Activities

RUAN Yawen, HUANG Peiling, YAN Jiangyu, LI Guorui, HUANG Jing

State Key Laboratory of Chemo/Biosensing and Chemometrics, School of Biomedical Sciences, Hunan University, Changsha 410082, P. R. China

Received:2022-03-31 Revised:2022-05-07 Online:2022-08-01 Published:2022-07-01
Contact: HUANG Jing E-mail:huangjing16@hnu.edu.cn
Supported by:
This work was supported by the National Natural Science Foundation of China (Nos.31871365, 22177029) and the Fundamental Research Funds for the Central Universities, China.

Abstract

Abstract: Targeted prodrug strategy, which utilizes the endogenous biomarkers in cancer cells as activators to release the active drug, has been well established either in the fundamental research or the clinical treatment. However, many prodrugs suffer from safety concern due to "off-target activation". Dual or multiple biomarkers triggered prodrug may provide an effective strategy to overcoming the "off-target effect". Melanoma cells have both high levels of reactive oxygen species(ROS) and tyrosinase(TYR), which makes them significantly different from other tumor cells and normal cells. Here we reported a series of quinazolinone-aryl boronic acid/ester-based prodrugs, which can be activated by the cascade of ROS and TYR and selectively kill melanoma cells. The structure-activity relationship(SAR) analysis revealed that mitochondria-targeting property was vital for their cytotoxicity and the dual activated effector played a significant role in their selectivity towards melanoma cells. Among these candidates, compound 4b showed the highest toxicity to B16, leading to an imbalance of the redox system in melanoma cells, causing mitochondrial DNA damage, and then promoting melanoma cells death.

Key words: Targeted prodrug, Melanoma, Cell death, Cascade activation

RUAN Yawen, HUANG Peiling, YAN Jiangyu, LI Guorui, HUANG Jing. Dual Diomarkers Triggered Prodrugs for Precise Treatment of Melanoma:Design, Synthesis and Activities[J]. Chemical Research in Chinese Universities, 2022, 38(4): 949-956.

References

[1] Wu G., Zhao T., Kang D., Zhang J., Song Y., Namasivayam V., Kongsted J., Pannecouque C., De Clercq E., Poongavanam V., Liu X., Zhan P., J. Med. Chem., 2019, 62, 9375
[2] Zhang J., Ning L., Huang J., Zhang C., Pu K., Chem. Sci., 2019, 11, 618
[3] Zawilska J., Wojcieszak J, Olejniczak A., Pharmacological Reports, 2013, 65, 1
[4] Johnstone T. C., Suntharalingam K., Lippard S. J., Chem. Rev., 2016, 116, 3436
[5] Cheng R., Meng F., Deng C., Klok H. A., Zhong Z., Biomaterials, 2013, 34, 3647
[6] Olbryt M., Postepy. Dermatol. Alergol., 2019, 36, 129
[7] Zhang Y., He X, Zhang Y., Zhao Y., Lu S., Peng Y., Lu L., Hu X., Zhan M., Chem. Eng. J., 2021, 424, 130171
[8] Peng H., Wang T, Li G., Huang J, Chem. J. Chinese Universities, 2021, 42(11), 3357
[9] Solem E., Tuczek F., Decker H., Angew. Chem. Int. Ed., 2016, 55, 2884
[10] Bolton J. L., Dunlap T., Chem. Res. Toxicol, 2017, 30, 13
[11] Ji Y., Dai F., Yan S., Shi J. Y., Zhou B., J. Agric. Food Chem., 2019, 67, 9060
[12] Pu Y., Zhou B., Xiang H., Wu W., Yin H., Yue W., Yin Y., Li H., Chen Y., Xu H., Biomaterials, 2020, 259, 120329
[13] Bao X. Z., Dai F., Wang Q., Jin X. L., Zhou B., Free Radic. Biol. Med., 2019, 134, 406
[14] Bai M., Huang J., Zheng X., Song Z., Tang M., Mao W., Yuan L., Wu J., Weng X., Zhou X., J. Am. Chem. Soc., 2010, 132, 15321
[15] Jawaid S., Khan T. H., Osborn H. M., Williams N. A., Anticancer Agents Med. Chem., 2009, 9, 717
[16] Purohit V., Simeone D. M., Lyssiotis C. A., Cancers (Basel), 2019, 11, 955
[17] Zhang W., Hu X., Shen Q., Xing D., Nat. Commun., 2019, 10, 1704
[18] Ding Z., Cen J, Wu Y, Zhong K, Liu G., Hu J., Liu S., Giant, 2020, 1, 100012
[19] Deng Z., Qian Y., Yu Y., Liu G., Hu J., Zhang G., Liu S., J. Am. Chem. Soc., 2016, 138, 10452
[20] Wang L., Xie S., Ma L., Chen Y., Lu W., Eur. J. Med. Chem., 2016, 116, 84
[21] Kim E. J., Bhuniya S., Lee H., Kim H. M., Cheong C., Maiti S., Hong K. S., Kim J. S., J. Am. Chem. Soc., 2014, 136, 13888
[22] Kuang Y., Balakrishnan K., Gandhi V., Peng X., J. Am. Chem. Soc., 2011, 133, 19278
[23] Reshetnikov V., Daum S., Janko C., Karawacka W., Tietze R., Alexiou C., Paryzhak S., Dumych T., Bilyy R., Tripal P., Schmid B., Palmisano R., Mokhir A., Angew. Chem. Int. Ed., 2018, 57, 11943
[24] Xu J., Zhang Y., Yu H., Gao X., Shao S., Anal. Chem., 2016, 88, 1455
[25] Ni Y., Liu H., Dai D., Mu X., Xu J., Shao S., Anal. Chem., 2018, 90, 10152
[26] Guo H., Aleyasin H., Dickinson B. C., Haskew-Layton R. E., Ratan R. R., Cell Biosci., 2014, 4, 64
[27] Li G., Yang Y, Zhang Y., Huang P., Yan J., Song Z., Yuan Q, Huang J., CCS Chemistry, 2021, 1622
[28] Peng H., Wang T., Li G., Huang J., Yuan Q., Anal. Chem., 2022, 94, 1070
[29] Wu X., Li L., Shi W., Gong Q., Ma H., Angew. Chem. Int. Ed., 2016, 55, 14728
[30] Liu S., Bu L., Zhang Y., Yan J., Li L., Li G., Song Z., Huang J., Anal. Chem., 2021, 93, 5267
[31] Chen W., Fan H., Balakrishnan K., Wang Y., Sun H., Fan Y., Gandhi V., Arnold L. A., Peng X., J. Med. Chem., 2018, 61, 9132
[32] Winder A. J., Harris H., Eur. J. Biochem., 1991, 198, 317
[33] Förster T, Angew. Chem. Int. Ed., 1969, 8, 333
[34] Li Y., Zhou H., Chen J, Shahzad S., Yu C, Biosens. Bioelectron., 2016, 76, 38
[35] Samuni A. M., Chuang E. Y., Krishna M. C., Stein W., Degraff W., Russo A., Mitchell J. B., Proc. Natl. Acad. Sci. USA, 2003, 100, 5390
[36] Felim A., Urios A., Neudörffer A., Herrera G., Blanco M., Largeron M., Chem. Res. Toxicol., 2007, 20, 685

Dual Diomarkers Triggered Prodrugs for Precise Treatment of Melanoma:Design, Synthesis and Activities

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 2

Recommended Articles

Metrics

Comments

[1]	LI Jun, OU Hanlin, DING Dan. Recent Progress in Boosted PDT Induced Immunogenic Cell Death for Tumor Immunotherapy [J]. Chemical Research in Chinese Universities, 2021, 37(1): 83-89.
[2]	TANG Xu, DU Zhijun, WU Guojie, HAN Fushe. Synthesis of P-Stereogenic Diarylphosphinamides as Novel Inhibitors of Melanoma [J]. Chemical Research in Chinese Universities, 2019, 35(5): 812-816.