Ahmed Al-Sheikh

This study aimed to synthesize and biologically evaluate novel 4-amino-6-phenoxyquinoline and 4,6-diphenoxyquinoline derivatives with potential anticancer activity. The newly synthesized compounds were screened for cytotoxicity against a panel of seven human cancer and normal cell lines using the MTT assay to determine IC₅₀ values, with sorafenib included as a reference drug. Among the tested molecules, compounds 7a and 7b demonstrated the most potent and selective reduction in cell viability, particularly in A549 lung carcinoma, PANC-1 pancreatic cancer, and MCF-7 breast cancer cells, and were therefore selected for further mechanistic investigations. Flow cytometry-based Annexin V/PI analysis revealed significant induction of apoptosis and necrosis following treatment, with pronounced effects observed in A549 and PANC-1 cells exposed to compound 7a and sorafenib. Acridine orange staining further confirmed a marked increase in autophagic activity across all examined cancer cell lines, indicating the activation of additional cell death pathways. Cell cycle analysis demonstrated compound- and cell-type-dependent effects, including S-phase arrest in A549 and PANC-1 cells and G1-phase arrest in MCF-7 cells. Collectively, these findings indicate that 4-amino-6-phenoxyquinoline derivatives exert anticancer effects through coordinated induction of apoptosis, autophagy, and cell cycle arrest, supporting their potential as promising candidates for further anticancer drug development.

Schematic summary of the design, synthesis, and biological evaluation of KA7, a novel quinolone-based sorafenib analogue demonstrating potent anticancer and immunomodulatory activities.

Cancer is a life-threatening illness all over the world, and developing anticancer treatments with high efficacy and low side effects remains a challenge. The quinoline ring structure has long been recognized as a flexible nucleus in the design and synthesis of physiologically active chemicals. In this study, five new 2-morpholino-4-anilinoquinoline compounds were synthesized and their biological anticancer potential against the HepG2 cell line was assessed. The compounds produced demonstrated varying responses against HepG2 cells, with compounds 3c, 3d, and 3e exhibiting the highest activity, with IC₅₀ values of 11.42, 8.50, and 12.76 μM, respectively. It is a critical requirement that anticancer medications are able to selectively decrease cancer growth while not causing damage to normal cells. Compound 3e exhibited increased activity while maintaining adequate selectivity. It was also the most effective chemical against cell migration and adhesion, which could play an important role in drug resistance and cell metastasis. In total, the findings revealed good possibilities for anticancer therapy, suggesting a target for future development of anticancer medication.

Reaction of 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene (1) with phthalimide, quinazolinedione, thiophenole and 4-pyridinethiole led to the formation of the hydrogen-bonded salts, imidazolium phthalimide (2), imidazolium quinazolinedione (3), imidazolium thiophenolate (4) and imidazolium 4-pyridinethiolate (5), respectively, in good yield. In crystals of 2, the anion is linked to the imidazolium cation by a C–H···O hydrogen bond, while in 3 and 5 C–H···N hydrogen bonds are observed. In 4, the imidazolium ion is linked to the anion by C–H···S hydrogen bonds. In compounds 2, 3 and 5, the interionic hydrogen bonds are close to linearity, while the interionic hydrogen bond angle in 4 is 148.5(9)°.

The synthesis of a molecularly diverse library of tetrasubstituted alkenes containing a barbiturate motif is described. Base-induced condensation of N¹-substituted pyrimidine-2,4,6(1H,3H,5H)-triones with 5-(bis(methylthio)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione gave 3-substituted 5-(methylthio)-2H-pyrano[2,3-d]pyrimidine-2,4,7(1H,3H)-triones (‘pyranopyrimidinones’), regioselectively. A sequence of reactions involving ring-opening of the pyran moiety, displacement of the methylthio group with an amine, re-formation of the pyran ring, and after its final cleavage with an amine, gave tetrasubstituted alkenes (3-amino-3-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)propanamides) with a diversity of substituents. Cleavage of the pyranopyrimidinones with an aniline was facilitated in 2,2,2-trifluoroethanol under microwave irradiation. Compounds were tested against Escherichia coli, Staphylococcus aureus, the yeast Schizosaccharomyces pombe, and the pathogenic fungus Candida albicans. No compounds exhibited activity against E. coli, whilst one compound was weakly active against S. aureus. Three compounds were strongly active against S. pombe, but none was active against C. albicans.

In this study analogues of compounds based on pyrano[2,3-d]pyrimidine were synthesized. 1,3-dimethyl-5- (thiomethyl)-2,4,7-trioxo-1,3,4,7-tetrahydro-2H-pyrano[2,3-d]pyrimidine-6-carboxylic acid 3 and 1,3-dimethyl-5- (thiomethyl)-2H-pyrano[2,3-d]pyrimidine-2,4,7(1H,3H)-trione 4 were obtained by the treatment of Triethylammonium 5- [(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)(thiomethyl)methyl]-1,3-dimethylpyrimidine-2,4,6-trionate 1 with methyl sulfonic acid and pyridine, respectively. 5,5-dianilino-1,3-dimethyl-5,6-dihydro-2H-pyrano[2,3-d]pyrimidine- 2,4,7(1H,3H)-trione 6 was obtained after oxidizing compound 4 to produce 1,3-dimethyl-5-(methylsulfinyl)-2Hpyrano[ 2,3-d]pyrimidine-2,4,7(1H,3H)-trione 5 , then the sulfoxide group on compound 5 was replaced by aniline group.

Hydrogen Bonds with Cyanide Ions? The Structures of 1,3‐Diisopropyl‐4,5‐dimethylimidazolium Cyanide and 1‐Isopropyl‐3,4,5‐trimethylimidazolium Cyanide1,3‐Diisopropyl‐4,5‐dimethylimidazolium cyanide (2a) and 1‐isopropyl‐3,4,5‐trimethylimidazolium cyanide (2b) are obtained from the reaction of the corresponding 2,3‐dihydrodimethylimidazol‐2‐ylidenes (1) and hydrogen cyanide in excellent yield. Their crystal structure analyses reveal the presence of ion pairs linked by hydrogen bonds. The crystal structure analysis of 2a reveals a near colinear orientation of the C(1)‐H bond axis and the cyanide ion while in 2b this orientation is perpendicular. In both cases, the interionic distances are in the expected range for hydrogen bonds. Ab‐initio calculations of the total energy of the salts 2 indicate small differences in energy between the colinear and perpendicular orientation of the ions as well as between the colinear C‐H···C‐N and C‐H···N‐C orientations. The comparison of calculated and measured ¹³C and ¹⁵N NMR chemical shifts does not allow the distinction between the possible orientations.