This work demonstrates the optimization of an efficient, mild, and environmentally friendly synthetic approach to access a diverse library of N-naphthoyl thioureas. These derivatives could be exploited as precursor scaffolds for designing valuable heterocycles with anticipated biological activities. Additionally, the utilization of a copper complex derived from the newly synthesized N-naphthoyl thiourea ligand in the photodegradation of methyl orange (MO) dye was explored. The antiproliferative effect of the synthesized derivatives was examined against MCF-7, HCT116, and A549 cancer cell lines. Most of the assembled derivatives revealed a significant cytotoxic effect, in some cases, greater than doxorubicin. Of these, the copper complex demonstrated significant antitumor activities (IC₅₀ < 1.3 μM) and lesser cytotoxic impact (IC₅₀ > 76 μM), indicating its possibility as a pioneering candidate for future carcinogenic pharmaceutics. Relations between the structure and activity also have been addressed.

The present work is mainly dedicated to heterocyclic compounds as well as S-glycoside. 1,4-dihydroquinoxaline derivatives 3 were obtained from the reaction 2 with carbon disulfide in presence of potassium hydroxide. S-glycoside 4 was prepared from the reaction of compound 3 with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide. Several heterocyclic derivatives containing thioxobenzo[g]pteridine ring systems were obtained starting from ethyl 3-amino-1,4-dihydroquinoxaline-2-carboxylate 1. These newly synthesized compounds were docked within the active site of cyclooxygenase-2 (COX-2). The results of this docking study revealed that the new compounds might exhibit good anti-inflammatory activity. The structure of new compounds was demonstrated by elemental analysis, IR, ¹H NMR spectra and mass spectra.

Novel derivatives of pyrimidinone ring carrying some five-membered heterocycles had been designed and prepared. 1,3-Thiazolidin-4-one derivative 7 was prepared by the reaction of 1,2,3,4-tetrahydro-4-(4-hydroxyphenyl)-6-methyl-N′-((naphthalen-4-yl)methylene)-2-oxopyrimidine-5-carbohydrazide 6 with thioglycolic acid. Reacting the hydrazide 5 with benzoyl chloride gave compound 8 which cyclized to 1,3,4-oxadiazole 9 by the use of phosphorus pentoxide. Moreover, the pyrazole derivative 10 was obtained from reacting compound 5 with ethyl acetoacetate. Furthermore, the reaction of the hydrazide 5 with phenyl isothiocyanates produced the carbothioamide 11 which refluxed with hydrazonoyl chloride to yield 1,3,4-thiadiazole derivative 14. In addition, 1, 2,4-triazole derivative 16 was prepared via reacting the carbothioamide 11 with sodium hydroxide followed by methylation with methyl iodide. The structures of the newly prepared heterocyclic compounds were determined by spectral and elemental analysis. The cytotoxic activity of the target compounds (7, 9, 10, 14, and 16) were estimated in vitro against PC-3 (prostate adenocarcinoma), human HepG-2 (liver carcinoma), and HCT116 (colorectal carcinoma) cell lines using MTT assay. All the tested compounds appeared high level of inhibition against PC-3 and HCT116 cell lines, while appeared weak inhibitory action against HepG-2 cell lines, especially, the thiadiazole derivative 14. Furthermore, docking study had been carried out on the targets 7, 9, 10, 14, and 16 within EGFR as a prediction for the anticancer activity. All the docked compounds showed good fitting with EGFR recording docking scores range (-27.99 to -19.01).

Direct preparation of 2-amino-5,6,7,8-tetrahydro-4-(4-methoxyphenyl)-7,7-dimethyl-5-oxo-4H-chromene-3-carbonitrile 2 and 1,2-diamino-1,4,5,6,7,8-hexahydro-4-(4-methoxyphenyl)-7,7-dimethyl-5-oxo-3-quinolinecarbonitrile 11, which were utilized as starting products for the synthesis of S-nucleoside analogues 10 and 15 and C-nucleoside analogues 12 and 13, is presented in the current study. The antibacterial and antifungal activities of these new compounds were evaluated. The structures of the new products were confirmed on the basis of elemental and spectral analysis results.

An efficient, microwave/ultrasound-irradiated synthesis of novel chromenopyrimidines has been established. 2-Amino-5-oxo-4-(thiophen-2-yl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (1) underwent cyclization reactions with various assorted reagents under sustainable conditions to afford a family of fused pyrimidine derivatives. The proposed structures of the designed fused pyrimidines were confirmed by several spectral techniques. Moreover, the targeted pyrimidines were estimated for their in vitro cytotoxic activities toward three carcinoma cell lines: breast (MCF7), hepatocyte (HepG2), and lung (A549) cancer cell lines, as well as one noncancerous cell line (MCF-10A). Structure-activity relationship (SAR) analyses revealed that derivatives 3 and 7 exhibited the highest potency in inhibiting the growth of cancer cells tested in vitro. Particularly, 3-amino-4-imino-5-(thiophen-2-yl)-3,4,5,7,8,9-hexahydro-6H-chromeno[2,3-d]pyrimidin-6-one (3) displayed a robust impact with IC₅₀ values ranging from 2.02 to 1.61 μM. Interestingly, compound 3 was observed to have low cytotoxicity toward noncancerous cell (MCF-10A) compared to the standard drug (Doxorubicin). Further, quantum chemical computations of the designed molecules utilizing density functional theory (DFT) were conducted and shown to be compatible with the observed antiproliferative properties. Thorough docking investigations revealed that the assembled compounds possess exceptionally low binding energies toward our three selected proteins: 4b3z-Lung, HepG2-2JW2, and 6ENV-MCV-7. Based on these intriguing results, compound 3 could be further evaluated for preclinical screening, potentially paving the way for its utilization as a promising cancer treatment.