A multifaceted approach for the development of novel Hantzsch 1,4-dihydropyridines as anticancer agents: Rational design, parallel synthesis, analysis, cytotoxicity and EGFR/HER2 inhibition studies

Dihydropyridines (DHPs) exhibit a wide range of pharmacological properties especially against cancer. In this context, a new series of 1,4-dihydropyridines were meticulously designed employing scaffold hybridization technique targeting the EGFR/HER2 receptors. The parallel synthesis of the designed dihydropyridines was achieved using the Hantzsch multiple component reactions. Following the synthesis, rigorous purification methods were carried out and elucidation of their chemical structures through comprehensive analytical techniques such as IR, NMR, and Mass Spectrometry. The initial synthetic step of acetoacetanilide formation was of less product yield contrasting with the satisfactory yields achieved for final multicomponent reactions. The synthesized ligands were subjected to screening against MCF-7 breast cancer and normal Vero cells to evaluate their potential anti-cancer activity. This assessment was carried out by quantifying cytotoxicity levels and structure activity relationships. Among them, compounds 6 and 14 exhibited the good inhibitory effects on the proliferation of MCF-7 cells with an IC50 value of 14.44 and 14.38 μM, respectively, which was quite closer to that of Lapatinib. Furthermore, the influence of ligands on target proteins expressions were assessed via flow cytometry experiments against EGFR & HER2. Computational studies were also performed to correlate the experimental results

Isolation, Identification, and Antibacterial Properties of Prodigiosin, a Bioactive Product Produced by a New <i>Serratia marcescens</i> JSSCPM1 Strain: Exploring the Biosynthetic Gene Clusters of <i>Serratia</i> Species for Biological Applications

Prodigiosin pigment has high medicinal value, so exploring this compound is a top priority. This report presents a prodigiosin bioactive compound isolated from Serratia marcescens JSSCPM1, a new strain. The purification process of this compound involves the application of different chromatographic methods, including UV-visible spectroscopy, high-performance liquid chromatography (HPLC), and liquid chromatography–mass spectrometry (LC/MS). Subsequent analysis was performed using nuclear magnetic resonance (NMR) to achieve a deeper understanding of the compound’s structure. Finally, through a comprehensive review of the existing literature, the structural composition of the isolated bioactive compound was found to correspond to that of the well-known compound prodigiosin. The isolated prodigiosin compound was screened for antibacterial activity against both Gram-positive and Gram-negative bacteria. The compound inhibited the growth of Gram-negative bacterial strains compared with Gram-positive bacterial strains. It showed a maximum minimum inhibitory concentration against Escherichia coli NCIM 2065 at a 15.9 ± 0.31 μg/mL concentration. The potential binding capabilities between prodigiosin and the OmpF porin proteins (4GCS, 4GCP, and 4GCQ) were determined using in silico studies, which are generally the primary targets of different antibiotics. Comparative molecular docking analysis indicated that prodigiosin exhibits a good binding affinity toward these selected drug targets