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The alkylation reaction was used to couple zerumbone with the 3-substituted quinazolinone-4(3H)-ones and quinolines, resulting in the formation of 11 new conjugates. Their structures were fully characterized by 1D-, 2D-NMR, and HRMS spectral data. The evaluation of their anti-inflammatory activity was examined by inhibiting NO production in RAW 267.4 cells. Screening for their cytotoxic activity was performed using three human cancer cell lines HepG2, SK-LU-1, and MCF-7. The results indicated that all 11 novel conjugates exhibited potent cytotoxic activity against the tested cell lines with IC50 values in the range of 1.01–9.86 µg/mL, which were stronger than those of the parent compound zerumbone. In silico EGFR inhibitory activity was also performed by docking and molecular dynamics simulation studies to find out the most potent compounds based on the main interactions of zerumbone derivatives 16a-k with important amino acids of EGFR (PDB ID 4HJO) protein in its active site.

CuSO4/hydrazine hydrate was used as a catalyst system for copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) of AZT and 5′-azido adenosine with terminal alkynes to give 30 novel 1,2,3-triazole derivatives. Screening for their anticancer, anti-inflammatory, angiotensin-converting enzyme 2 (ACE2), and 3C-like protease (3CLpro) inhibitory activities showed that several triazoles of AZT containing murayafoline A and indirubin-3′-oxime inhibited the growth of HepG2 and LU-1 with the IC50 values ranging from 11.01 to 19.87 μg/mL. Besides that, some triazole derivatives of adenosine exhibited anti-inflammatory activity against RAW264.7 cells with the IC50 values within an interval of 12.00–59.48.00 μg/mL. Especially, two triazoles of adenosine with indirubin-3′-oxime at O- and N1 positions expressed the ACE2 and 3CLpro inhibitory activities in which the triazole of adenosine with indirubin-3′-oxime at N1 inhibited both ACE2 and 3CLpro inhibitory activities with IC50 values of 135.62 and 142.95 μg/mL, respectively.