Dipeptidyl peptidase IV (DPP-IV) is a serine protease whose inhibition has been an object of considerable interest in the context of developing novel treatments for type 2 diabetes mellitus. The development of novel DPP-IV inhibitors from natural or synthetic origin has seen a growing scientific interest in recent years, especially during the SARS-CoV-2 pandemic, when DPP-IV inhibitors were found to be of beneficial therapeutic value for COVID-19 patients. The present manuscript aims to summarize the most recent information on the synthesis of different DPP-IV inhibitors, emphasizing the various heterocyclic scaffolds that can be found in them. Special attention is devoted to DPP-IV inhibitors that are currently in clinical trials. Different synthetic approaches for the construction of DPP-IV inhibitors are discussed, as well as the most recent developments in the field.

Recent studies have discovered that aryl-substituted pyrido[2,1-a]isoquinolines have the potential to be highly active DPP IV inhibitors. In previous studies, we reported a novel synthetic approach for the construction of their sulfur-containing bioisosteric [1,4]thiazino[3,4-a]isoquinolines analogues, incorporating an additional aryl substituent. The present study aims to investigate the DPP IV inhibitory activity and cytotoxicity of the synthesized molecules by in vitro assay. The geometry optimization and molecular docking of the synthesized compounds were used to determine their binding modes to the active site of DPP IV. The docking analysis revealed that the energy-minimized poses of the studied compounds are close to the most important selectivity cliffs for DPP IV inhibition, forming hydrogen bonds and hydrophobic interactions with them. These results can be considered as a preliminary step towards further structural activity modifications.

A new series of styryl hemicyanine dyes featuring substituted N-phenylpiperazine end groups was synthesized using an environmentally friendly procedure. The photophysical properties of the dyes were systematically investigated in organic solvents of varying polarity and when bound to DNA, using a combination of spectroscopic techniques. The dyes show strong negative solvatochromism and exhibit fluorescence quenching upon DNA binding. The dyes are definitely halochromic, exhibiting pronounced fluorescent acidochromism, accompanied by a photoinduced electron transfer (PET) effect. Titration with acid of the dye–DNA complexes restores fluorescence, indicating suppression of the PET and, at the same time, rigidizing of the chemical structure. UV/VIS and fluorescence titration, circular dichroism spectroscopy, and molecular docking methods were used to investigate the interaction mode between the dyes and DNA. Density functional theory (DFT) and time-dependent density functional theory (TDDFT) quantum chemical calculations were employed in deciphering the observed spectroscopic behavior and PET-related effects. The obtained results suggest the dyes’ potential as pH-responsive fluorescent probes for nucleic acid environments.

Prostate cancer is one of the leading causes of death among men. Our study focuses on seeking new compounds and combinations to diminish the severe side effects of classical anticancer drugs for treating this type of cancer. In this study, we investigated and compared the classical anticancer drug docetaxel and non-classical compounds, Au porphyrin, and the plant lectin jacalin, and in different combinations on the prostate cancer cell line PC3. Jacalin, isolated from jackfruit seeds by affinity chromatography on immobilized galactose, specifically recognizes the tumor-associated Thomsen–Friedenreich antigen. The present investigation shows the interaction of jacalin with Au porphyrin, registering conformational changes within the protein due to the binding. From the titration curve, the affinity of 1.8 ± 0.39 µM for the jacalin—Au porphyrin complex was calculated. In vitro experiments with PC3 cells treated with docetaxel, Au porphyrin, jacalin and combinations indicated a decrease in cell viability. The IC₅₀ for Au porphyrin and for docetaxel were studied and indicated that the calculated IC₅₀ for docetaxel was 8 orders of magnitude higher than that for Au porphyrin. Interestingly, we found that jacalin-Au porphyrin complex is more cytotoxic reaching cell viability of 34%, than docetaxel-Au-porphyrin complex (with cell viability above 50%). Our results demonstrate the effects of three compounds as well as the effects of their combinations upon PC3 cells. Interestingly, low concentrations of the plant lectin jacalin (3 µM) facilitated the cell cytotoxicity of Au-porphyrin, showing new perspectives in cancer treatment.

The synthesis of the compound 9,10-dimethoxy-4-oxo-1-phenyl-1,3,4,6,7,11b-hexahydro-[1,4]thiazino[3,4-a]isoquinoline-1-carboxylic acid (4) was described for the first time using a reaction between 6,7-dimethoxy-3,4-dihydroisoquinoline and phenyl-substituted thiodiacetic anhydride 3. The reaction proceeded in excellent yield and furnished the compound 4 as a single diastereomer. The structure and relative configuration of 4 was elucidated using a combination of spectroscopic techniques–¹H, ¹³C, COSY, HSQC, HMBC, and NOESY NMR spectra, as well as elemental analysis.