ELECTROPHILIC ORGANOSELENIUM COMPOUNDS AND SARS-COV-2: PRO-OXIDANT ACTIVITY AS A MORE PROMISING WAY TOWARDS THE DRUGGABILITY

1st International Conference on Chemo and BioInformatics, ICCBIKG  2021, (20-25)

AUTHOR(S) / АУТОР(И): Claudio Santi, Luca Sancineto, Francesca Mangiavacchi, Cecilia Scimmi, Sougat Misra

E-ADRESS / Е-АДРЕСА: claudio.santi@unipg.it

Download Full Pdf   

DOI: 10.46793/ICCBI21.020S

ABSTRACT / САЖЕТАК:

Ebselent has been recently reported as the most efficient hinibitors of Sars-Cov-2 main protease (Mpro) thought the electrophilic covalent pro-oxidation of the reactive Cysteine 145. According to similar evidences in literature we can propose a general mechanism to explore a novel and promising application of mild organoselenium centered electrophiles in medicinal chemistry. New insights in the field of covalent and non-covalent inhibition of Mpro as well as the antiviral SARS-Cov2 activity of novel organoselenium compounds will be here discussed

KEY WORDS / КЉУЧНЕ РЕЧИ:

Selenium, Covid-19, SARS-Cov2, electrophiles

REFERENCES / ЛИТЕРАТУРА:

  • Gonzalez-Flores, S. P. Shetty, A. Dubey and P. R. Copeland, BioMolecular Concepts, 2013, 4, 349–365.
  • M. Barcellos, L. Abenante, M. T. Sarro, I. Di Leo, E. J. Lenardão, G. Perin and C. Santi, Curr. Org. Chem., 2017, 21, 2044–2061.
  • Mugesh and H. B. Singh, Chemical Society Reviews, 2000, 29, 347–357.
  • Obieziurska-Fabisiak, A. J. Pacuła, L. Capoccia, J. Drogosz-Stachowicz, A. Janecka, C. Santi and J. Ścianowski, Molecules, 2020, 25, 3354.
  • Flohe, W. A. Günzler and H. H. Schock, FEBS Letters, 1973, 32, 132–134.
  • Chaudiere, E. C. Wilhelmsen, L. Tappel, J Biol Chem, 1984, 259, 1043-1050
  • C. Ranu and B. Banerjee, Eds., in Organoselenium Chemistry, De Gruyter, 2020, pp. 381–422.
  • Bhowmick, S. Srivastava, P. D’Silva and G. Mugesh, Angewandte Chemie International Edition, 2015, 54, 8449–8453.
  • Mugesh, Current Chemical Biology, 2013, 7, 47–56.
  • Santi, C. Tidei, C. Scalera, M. Piroddi and F. Galli, Current Chemical Biology, 2013, 7, 25–36.
  • J. Pacuła, F. Mangiavacchi, L. Sancineto, E. J. Lenardão, J. Ścianowski and C. Santi, Current Chemical Biology, 2016, 9, 97–112.
  • Orian and S. Toppo, Free Radical Biology and Medicine, 2014, 66, 65–74.
  • J. Reich and R. J. Hondal, ACS Chemical Biology, 2016, 11, 821–841.
  • K. Sarma and G. Mugesh, Journal of the American Chemical Society, 2005, 127, 11477–11485.
  • Gandin, P. Khalkar, J. Braude and A. P. Fernandes, Free Radical Biology and Medicine, 2018, 127, 80–97.
  • H.Lee, D. Jeong, Molecular Medicine Reports, 2012, 5, 299-304.
  • Sancineto, A. Mariotti, L. Bagnoli, F. Marini, J. Desantis, N. Iraci, C. Santi, C. Pannecouque and O. Tabarrini, Journal of Medicinal Chemistry, 2015, 58, 9601–9614.
  • Chiou, S. Wan, K.-F. Chan, P.-K. So, D. He, E. W. Chan, T. Chan, K. Wong, J. Tao and S. Chen, Chemical Communications, 2015, 51, 9543–9546.
  • Macegoniuk, E. Grela, J. Palus, E. Rudzińska-Szostak, A. Grabowiecka, M. Biernat and Ł. Berlicki, Journal of Medicinal Chemistry, 2016, 59, 8125–8133.
  • Bartolini, J. Commodi, M. Piroddi, L. Incipini, L. Sancineto, C. Santi and F. Galli, Free Radical Biology and Medicine, 2015, 88, 466–480.
  • S. Galant, J. Rafique, A. L. Braga, F. C. Braga, S. Saba, R. Radi, J. B. T. da Rocha, C. Santi, M. Monsalve, M. Farina and A. F. de Bem, Neurochemical Research, , DOI:10.1007/s11064-020- 03026-x.
  • Jin, X. Du, Y. Xu, Y. Deng, M. Liu, Y. Zhao, B. Zhang, X. Li, L. Zhang, C. Peng, Y. Duan, J. Yu, L. Wang, K. Yang, F. Liu, R. Jiang, X. Yang, T. You, X. Liu, X. Yang, F. Bai, H. Liu, X. Liu, W. Guddat, W. Xu, G. Xiao, C. Qin, Z. Shi, H. Jiang, Z. Rao and H. Yang, Nature, 2020, 582, 289–293.
  • Sies and M. J. Parnham, Free Radical Biology and Medicine, 2020, 156, 107–112.
  • Węglarz-Tomczak,      J.       M.       Tomczak,      M.       Talma      and       S.       Brul, bioRxiv 2020.05.17.100768; doi: https://doi.org/10.1101/2020.05.17.100768
  • Renson, E. Etschenberg, J. Winkelmann, US patent 4, 352, 799 (1982) [21] E. Lynch, J. Kil, Semin. Hear, 2009, 30, 047–055.
  • Kil, E. Lobarinas, C. Spankovich, S. K. Griffiths, P. J. Antonelli, E. D. Lynch and C. G. Le Prell, The Lancet, 2017, 390, 969–979.
  • Masaki, A. L. Sharpley, C. M. Cooper, B. R. Godlewska, N. Singh, S. R. Vasudevan, C. J. Harmer, G. C. Churchill, T. Sharp, R. D. Rogers and P. J. Cowen, Psychopharmacology, 2016, 233, 2655–2661.
  • Nascimento, P. S. Cordeiro, M. Arca, F. Marini, L. Sancineto, A. L. Braga, V. Lippolis, M. Iwaoka and C. Santi, New Journal of Chemistry, 2020, 44, 9444–9451.
  • Luo, L. Liang, J. Sheng, Y. Pang, J. Li, L. Huang and X. Li, Bioorganic & Medicinal Chemistry, 2014, 22, 1355–1361.
  • J. Pacuła, K. B. Kaczor, J. Antosiewicz, A. Janecka, A. Długosz, T. Janecki, A. Wojtczak and
  1. Ścianowski, Molecules, 2017, 22, 492