γ-Glutamyltranspeptidase (GGT) Sensitive Fluorescence Probes for Cancer Diagnosis; Brief Review.

Millions of deaths occur each year due to the late diagnosis of abnormal cellular growth within the body. However, the devastating impact of this can be significantly reduced if cancer metastasis is detected early through the use of enzymatic biomarkers. Among several biomarkers, γ-glutamyltranspeptidase (GGT) stands out as a member of the aminopeptidase family. It is primarily found on the surface of cancer cells such as glioma, ovarian, lung, and prostate cancer, without being overexpressed in normal cells or tissues. Recent years have witnessed significant progress in the field of cancer monitoring and imaging. Fluorescence sensing techniques have been employed, utilizing organic small molecular probes with enzyme-specific recognition sites. These probes emit a fluorescent signal upon interacting with GGT, enabling the imaging, identification, and differentiation of normal and cancerous cells, tissues, and organs. This review article presents a concise overview of recent progress in fluorescent probes developed for the selective detection of GGT, focusing on their applications in cancer imaging. It highlights the observed alterations in the fluorescence and absorption spectra of the probes before and after interaction with GGT. Additionally, the study investigates the changes in the probe molecule's structure following enzyme treatment, evaluates the sensor's detection limit, and consolidated imaging studies conducted using confocal fluorescence analysis. This comprehensive survey is expected to contribute to the advancement of sensing techniques for biomarker detection and cancer imaging, providing valuable insights for refining methodologies and inspiring future developments in this field.

2-Aminothiazole-Oxadiazole Bearing N-Arylated Butanamides: Convergent Synthesis, Tyrosinase Inhibition, Kinetics, Structure-Activity Relationship, and Binding Conformations.

A multi-step synthesis of novel bi-heterocyclic N-arylated butanamides was consummated through a convergent strategy and the structures of these medicinal scaffolds, 7a-h, were corroborated using spectral techniques. The in vitro analysis of these hybrid molecules revealed their potent tyrosinase inhibition as compared to the standard used. The kinetics mechanism was investigated through Lineweaver-Burk plots which exposed that, 7f, inhibited tyrosinase enzyme non-competitively by forming the enzyme-inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 0.025 µM. Their binding conformations were ascertained by in silico computational studies whereby these molecules disclosed good binding energy values (kcal/mol). So, it was anticipated from the current research that these bi-heterocyclic butanamides might be probed as imperative therapeutic agents for melanogenesis.

Synthesis, Biological Evaluation, Migratory Inhibition and Docking Study of Indenopyrazolones as Potential Anticancer Agents.

Some bioactive derivatives of indeno[1,2-c]pyrazolones were synthesized through the reaction of phenylhydrazine, different aldehydes and indan-1,2,3-trione at room temperature in acetonitrile. Analytical and spectroscopic studies have confirmed the structural characteristics of the synthesized compounds. In addition, the target compounds were screened for the in-vitro antiproliferative properties against the B16F10 melanoma cancer cell lines by the standard MTT assay. The effect on inflammatory marker cyclooxygenase 2 and matrix metalloproteinase 2, 9 was also checked to determine the anti-inflammatory and anti-cell migratory properties of these compounds. The final compounds were also tested for their tyrosinase inhibitory activity. Among all compounds, screened for anticancer activity, three compounds 4e, 4f and 4h reduced the cell proliferation significantly comparable to that of the positive standard drug erlotinib (IC50 =418.9±1.54 µM) with IC50 values ranging from 20.72-29.35 µM. The compounds 4c-4h decreased the COX-2 expression whereas the MMP 2, 9 expressions were significantly reduced by 4a, 4b and 4h. This was confirmed by molecular docking studies, as 4e, 4f and 4h displayed good interactions with the active site of BRAF protein. The compounds 4b, 4f and 4h exhibited moderate tyrosinase inhibition effect as compared to α-MSH. Collectively, compound 4h can be considered as a candidate for further optimization in the development of anticancer therapies based on the results of biological investigations in this study.

Elastase inhibitory activity of quinoline Analogues: Synthesis, kinetic mechanism, cytotoxicity, chemoinformatics and molecular docking studies.

Herein, we have synthesized quinoline united various Schiff base derivatives (Q1-Q13) and systematically characterized them using diverse analytical practices such as 1H NMR, 13C NMR, FT-IR and LC-MS respectively. All of the target compounds that have been synthesized were tested for elastase inhibition, and the findings were compared to the standard drug oleanolic acid. Among the entire series, compound Q11 (IC50 = 0.897 ± 0.015 µM) exhibit most promising elastase inhibitory activity than oleanolic acid (Standard) having an IC50 value of 13.426 ± 0.015 µM. Also, the utmost effectivecompound Q11 was used for kinetic mechanism investigation based on in-vitro data, from which it has been concluded that compound Q11 inhibits elastase competitively. Furthermore, utilizing the MTT test approach, the most effective compounds were assessed for cytotoxicity on B16F10 melanoma cells. From the cytotoxicity experiment, the most potent compound did not display any hazardous response against B16F10 melanoma cells despite being treated at high concentrations. Additionally, the molecular docking study was settled to govern the binding interaction pattern among an enzyme and inhibitors.