Fe-MIL-88B-NH₂ has been co-loaded with α-tocopheryl succinate (TOS) and curcumin (CCM). The incorporation of TOS into the structure of Fe-MIL-88B-NH₂ improves cytotoxicity and apoptosis induction in the HeLa cell line.

Abstract

One of the strategies for improved therapeutic effects in cancer therapy is combination chemotherapy. In this study, a flexible nano-MOF (Fe-MIL-88B-NH₂) was synthesized in a sonochemical process, then co-loaded with α-tocopheryl succinate (TOS) and curcumin (CCM). The anticancer activity of co-loaded Fe-MIL-88B-NH₂ (Fe-MIL-88B-NH₂/TOS@CCM) against the HeLa cells was compared with that of the single-loaded counterpart (Fe-MIL-88B-NH₂@CCM). MTT analysis indicates improved cytotoxicity of Fe-MIL-88B-NH₂/TOS@CCM. The data from the cell apoptosis assay indicated more apoptosis in the case of the co-loaded nano-MOF. This study indicates the positive effect of the presence of TOS on enhancing the anticancer effect of Fe-MIL-88B-NH₂@CCM to prepare a more efficient drug delivery nanosystem.

The COVID-19 pandemic has brought a widespread influence on the world, especially in the face of sudden coronavirus infections, and there is still an urgent need for specific small molecule therapies to cope with possible future pandemics. The pathogen responsible for this pandemic is SARS-CoV-2, and understanding its structure and lifecycle is beneficial for designing specific drugs of treatment for COVID-19. The main protease (Mpro) which has conservative and specific advantages is essential for viral replication and transcription. It is regarded as one of the most potential targets for anti-SARS-CoV-2 drug development. This review introduces the popular knowledge of SARS-CoV-2 in drug development and lists a series of design principles and relevant activities of advanced Mpro inhibitors.

We have studied adenosine binding specificities of two bacterial DNA methyltransferases Taq methyltransferase (M.TaqI), and HhaI methyltransferase (M.HhaI). While these DNA methyltransferases have similar cofactor binding pocket interactions, experimental data showed different specificity for novel cofactors ((SNM) (S-guanosyl-L-methionine (SGM), S-cytidyl-L-methionine (SCM), S-uridyl-L-methionine (SUM)).Protein dynamics corroborate the experimental data on the cofactor specificities. For M.TaqI the specificity for S-adenosyl-L-methionine (SAM) is governed by the tight binding on the nucleoside part of the cofactor, while for M.HhaI the degree of freedom of the nucleoside chain allows the acceptance of other bases. The experimental data proves a catalytically productive methylation by M.HhaI binding pocket for all the SNM (S-nucleobase-L-methionine). Our results suggest a new route for successful design of unnatural SNM analogues for methyltransferases as a tool for cofactor engineering.