Synthesis and characterization of ferrocene-based thiosemicarbazones along with their computational studies for potential as inhibitors for SARS-CoV-2

Embargo End Date
2022-07-30

Type
Article

Authors
Jawaria, Rifat
Khan, Muhammad Usman
Hussain, Mazhar
Muhammad, Shabbir
Sagir, Muhammad
Hussain, Amjad
Al-Sehemi, Abdullah G.

Online Publication Date
2021-07-26

Print Publication Date
2022-03

Date
2021-07-26

Abstract
Graphical abstract Ferrocene and its derivatives are vital class of organometallic compounds having extensive biological activities. Six novel ferrocene-based thiosemicarbazones have been synthesized through the condensation reaction of acetyl ferrocene with differently substituted thiosemicarbazide. Furthermore, we used state-of-the-art computational docking approach to explore the theoretical aspects for possible antiviral potential of our synthesized compounds. All the six compounds were docked with Mpro protein of SARS-CoV-2, which is very crucial protein for viral replication. Among the six derivatives, compounds 2 and 4 showed higher binding affinities with binding energy of − 6.7 and − 6.9 kcal/mol, respectively. The visualization of intermolecular interactions between synthesized derivatives and Mpro protein illustrated that each of compounds 2 and 4 forms two hydrogen bonds accompanied by important hydrophobic interactions. The comparison of binding affinities with some recently approved drugs like remdesivir, chloroquine and hydroxychloroquine molecules are also made. The calculated binding energies of remdesivir, chloroquine and hydroxychloroquine molecules with Mpro of COVID-19 was found to be − 7.00, − 5.20 and − 5.60 kcal/mol, respectively. The binding energy of compound 4 (− 6.9 kcal/mol) was almost equal to the remdesivir and greater than the binding energies of chloroquine and hydroxychloroquine. It is expected from the current investigation that our synthesized ferrocene-based thiosemicarbazones might have potential for drug against SARS-CoV-2. Supplementary Information The online version contains supplementary material available at 10.1007/s13738-021-02346-1.

Citation
Jawaria, R., Khan, M. U., Hussain, M., Muhammad, S., Sagir, M., Hussain, A., & Al-Sehemi, A. G. (2021). Synthesis and characterization of ferrocene-based thiosemicarbazones along with their computational studies for potential as inhibitors for SARS-CoV-2. Journal of the Iranian Chemical Society. doi:10.1007/s13738-021-02346-1

Acknowledgements
The authors from King Khalid University extend their appreciations to Deanship of Scientific Research at King Khalid University for funding the work through Research Project (GRP/211/42). For computer time, this research used the resources of the Supercomputing Laboratory at King Abdullah University of Science & Technology (KAUST) in Thuwal, Saudi Arabia.

Journal
Journal of the Iranian Chemical Society

DOI
10.1007/s13738-021-02346-1

PubMed Central ID
PMC8311418

Additional Links
https://link.springer.com/article/10.1007/s13738-021-02346-1#Ack1

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