Synthesis, cytotoxicity, anti-inflammatory, anti-metastatic and anti-oxidant activities of novel chalcones incorporating 2-phenoxy-N-arylacetamide and thiophene moieties: induction of apoptosis in MCF7 and HEP2 cells.

Eight Novel chalcones were synthesized and their structures were confirmed by different spectral tools. All the prepared compounds were subjected to SRB cytotoxic screening against several cancer cell lines. Compound 5c exerted the most promising effect against MCF7 and HEP2 cells with IC50 values of 9.5 and 12 µg/mL, respectively. Real-time PCR demonstrated the inhibitory effect of compound 5c on the expression level of Antigen kiel 67 (KI-67), Survivin, Interleukin-1beta (IL-1B), Interleukin-6 (IL-6), Cyclooxygenase-2 (COX-2) and Protein kinase B (AKT1) genes. Flow-cytometric analysis of the cell cycle indicated that compound 5c stopped the cell cycle at the G0/G1 and G2/M phases in MCF7 and HEP2 treated cells, respectively. ELISA assay showed that Caspase 8, Caspase 9, P53, BAX, and Glutathione (GSH) were extremely activated and Matrix metalloproteinase 2 (MMP2), Matrix metalloproteinase 9 (MMP9), BCL2, Malondialdehyde (MDA), and IL-6 were deactivated in 5c treated MCF7 and HEP2 cells. Wound healing revealed that chalcone 5c reduced the ability to close the scrape wound and decreased the number of migrating MCF7 and HEP2 cells compared to the untreated cells after 48 h. Theoretical molecular modeling against P53 cancer mutant Y220C and Bcl2 showed binding energies of -22.8 and -24.2 Kcal/mole, respectively, which confirmed our ELISA results.

Novel Bis(2-cyanoacrylamide) Linked to Sulphamethoxazole: Synthesis, DNA Interaction, Anticancer, ADMET, Molecular Docking, and DFT Studies.

In the light of advancement and potential extensive use of medication design and therapy, new bis(cyanoacrylamides) incorporating sulphamethoxazole derivatives (7 a-7 f) were synthesized and confirmed by different spectral tools. In vitro anticancer activity towards different human cancer cells (HCT116, MDA-MB-231 and A549) was assessed using MTT assay. Among all derivatives, 4C- and 6C-spacer derivatives (7 e and 7 f) had the most potent growth inhibitory activities against HCT116 cells with IC50 values of 39.7 and 28.5 µM, respectively. 7 e and 7 f induced apoptosis and suppressed migration of HCT116 cells. These compounds also induced a significant increase in caspase-3 and CDH1 activities, and a downregulation of Bcl2 using ELISA. pBR322 DNA cleavage activities of cyanoacrylamides were determined using agarose gel electrophoresis. Furthermore, 7 e and 7 f showed good DNA and BSA binding affinities using different spectroscopic techniques. Furthermore, molecular docking for 7 e and 7 f was performed to anticipate their binding capabilities toward various proteins (Bcl2, CDH1 and BSA). The docking results were well correlated with those of experimental results. Additionally, density functional theory and ADMET study were performed to evaluate the molecular and pharmacokinetic features of 7 e and 7 f, respectively. Thus, this work reveals promising antitumor lead compounds that merit future research and activity enhancement.

Synthesis of Novel Diphenyl Ether-Based Bis-Heterocycles as Novel Hybrid Molecules via Michael and Other Cyclocondensation Reactions.

Molecular hybridization is a technique used in drug creation that involves combining the pharmacophoric moieties of multiple bioactive compounds to create a new hybrid molecule with better affinity and effectiveness. In this regard, we created unique hybrid molecules out of diphenyl ether-linked fused pyrans and other heterocycles. The Michael reaction of 4,4'-oxydibenzaldehyde with malononitrile and various active methylene derivatives, as well as enaminone derivatives, produced the matching bis-fused pyrans and fused pyridines, both connected to a diphenyl ether moiety. Furthermore, the acid-catalyzed reaction of 4,4'-oxydibenzaldehyde with dimedone or ß-naphthol produced the corresponding new bis(hexahydro-1H-xanthene-1,8-dione) and bis(14H-dibenzo[a,j]xanthene). The processes by which the target products are formed were also examined.

Synthesis of novel star-shaped molecules based on a 1,3,5-triazine core linked to different heterocyclic systems as novel hybrid molecules.

The synthesis of novel star-shaped compounds based on an s-triazine core and linked to hexahydroacridinediones, pyrimido[4,5-b]quinolones, 1H-isoquinolino[2,1-a]quinolines, tetrahydro-4H-chromenes, dihydropyrano[2,3-c]pyrazoles, thiazole, or benzothiazole as new hybrid molecules through Michael and Hantzsch reactions is reported. For this purpose, 2,4,6-tris(4-formylphenoxy)benzaldehyde was used as a versatile precursor.

An overview on synthetic strategies for the construction of star-shaped molecules.

Strategies for the synthesis of star-shaped molecules have been in high demand in the last decades due to the importance of those compounds in various fields. The distinctly different properties of these compounds compared to their linear analogues make them versatile building blocks for the formation of mesophases of interesting mesomorphic and photophysical properties. Moreover, the applications of star-shaped molecules as building units for dendrimers as well as in supramolecular host-guest chemistry have also been recently studied. The star-shaped molecules mentioned in this review are classified according to the central core as well as the type of side arms. The properties and applications of these compounds are described in the appropriate contexts. This report summarizes the recent advances in this area.