Vitamin B12 plays a key role in DNA stability. Research indicates that vitamin B12 deficiency leads to indirect DNA damage, and vitamin B12 supplementation may reverse this effect. Vitamin B12 acts as a cofactor for enzymes such as methionine synthase and methylmalonyl-CoA mutase, which are involved in DNA methylation and nucleotide synthesis. These processes are essential for DNA replication and transcription, and any impairment can result in genetic instability. In addition, vitamin B12 has antioxidant properties that help protect DNA from damage caused by reactive oxygen species. This protection is achieved by scavenging free radicals and reducing oxidative stress. In addition to their protective functions, cobalamins can also generate DNA-damaging radicals in vitro that can be useful in scientific research. Research is also being conducted on the use of vitamin B12 in medicine as vectors for xenobiotics. In summary, vitamin B12 is an essential micronutrient that plays a vital role in DNA stability. It acts as a cofactor for enzymes involved in the synthesis of nucleotides, has antioxidant properties and has potential value as a generator of DNA-damaging radicals and drug transporters.

The classical low-molecular-weight drugs are designed to bind with high affinity to the biological targets endowed with receptor or enzymatic activity, and inhibit their function. However, there are many non-receptor or non-enzymatic disease proteins that seem undruggable using the traditional drug approach. This limitation has been overcome by PROTACs, bifunctional molecules that are able to bind the protein of interest and the E3 ubiquitin ligase complex. This interaction results in the ubiquitination of POI and subsequent proteolysis in the cellular proteasome. Out of hundreds of proteins serving as substrate receptors in E3 ubiquitin ligase complexes, current PROTACs recruit only a few of them, including CRBN, cIAP1, VHL or MDM-2. This review will focus on PROTACs recruiting CRBN E3 ubiquitin ligase and targeting various proteins involved in tumorigenesis, such as transcription factors, kinases, cytokines, enzymes, anti-apoptotic proteins and cellular receptors. The structure of several PROTACs, their chemical and pharmacokinetic properties, target affinity and biological activity in vitro and in vivo, will be discussed. We will also highlight cellular mechanisms that may affect the efficacy of PROTACs and pose a challenge for the future development of PROTACs.

A series of variously functionalized selenium-containing compounds were purposely synthesized and evaluated against a panel of cancer cell lines. Most of the compounds showed an interesting cytotoxicity profile with compound 5 showing a potent activity on MCF7 cells. The ethyl amino derivative 5 acts synergistically with cis-platin and inhibits the GST enzyme with a potency that well correlates with the cytotoxicity observed in MCF7 cells. A computational analysis suggests a possible binding mode on the GST enzyme. As the main outcome of the present study, the ethyl amino derivative 5 emerged as a valid lead compound for further, future developments.

The results of our previous research indicated that some derivatives of benzofurans, particularly halogeno-derivatives, are selectively toxic towards human leukemia cells. Continuing our work with this group of compounds we here report new data on the synthesis as well as regarding the physico-chemical and biological characterization of fourteen new derivatives of benzofurans, including six brominated compounds. The structures of all new compounds were established by spectroscopic methods (¹H- and, ¹³C-NMR, ESI MS), and elemental analyses. Their cytotoxicity was evaluated against K562 (leukemia), MOLT-4 (leukemia), HeLa (cervix carcinoma), and normal cells (HUVEC). Five compounds (1c, 1e, 2d, 3a, 3d) showed significant cytotoxic activity against all tested cell lines and selectivity for cancer cell lines. The SAR analysis (structure-activity relationship analysis) indicated that the presence of bromine introduced to a methyl or acetyl group that was attached to the benzofuran system increased their cytotoxicity both in normal and cancer cells.