triazolo[3,4-a]isoquinolin-3-yl)ethan-1-ones 4 were prepared via reaction of C-acetylmethanohydrazonoyl chlorides 1A,B with 6,7-dimethoxy-3,4dihydroisoquinoline 3. Treatment of the latter products 4 with 3-aryl-1-phenyl-1H-pyrazole-4-carbaldehyde derivatives 5 in ethanol in the presence of sodium hydroxide solution at room temperature afforded chalcones 6.Cytotoxic assay was performed for in vitro antitumor screening against caucasian breast adenocarcinoma (MCF7) and hepatocellular carcinoma (HepG2) cell lines.Chalcones 6Ab and 6Ba have promising cytotoxic effects against MCF7 with IC50 values 8.0 and 7.5 µg/mL, respectively. Molecular docking using Mcule.com was carried out, for the most potent compounds 6Ab and 6Ba, against two protiens which are EGFR and DHFR.

Refluxing of enaminonitrile 3 with arylacetonitriles 2 in ethanol in the presence of piperidine afforded 4H-pyrido[2,1-a]isoquinoline-1-carbonitriles 6.Refluxing of 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)acetonitrile 1 with ethyl 3-aryl-2-cyanoacrylates 9 in acetonitrile in the presence of piperidine gave the corresponding 4H-pyrido[2,1-a]isoquinoline-1,3-dicarbonitriles 13. All the new synthesized compounds were identified by elemental analysis and spectral data. Cytotoxic assay was investigated for in vitro antitumor screening against MCF7, HepG2 and HCT-116 cell lines. Molecular docking using Mcule.com. software was carried out for the most potent compound 6b. The results are compared with doxorubicin standard anticancer drug. Antimicrobial activities were investigated, and all compounds revealed no antimicrobial activities against all tested strains except compounds 13b and 13e.

The in vitro antibacterial activity of brand‐new fused pyrido[2,1‐a]isoquinoline compounds was investigated. The desired pyrido[2,1‐a]isoquinoline derivatives 5, 9, and 10 were obtained by heating 2‐(6,7‐dimethoxy‐3,4‐dihydroisoquinolin‐1‐yl)acetonitrile 1 with ethylacetate derivatives 2, 6, and 7 in refluxing acetonitrile, while piperidine was present as a catalytic quantity. Under the same conditions, compound 1 was refluxed with compounds 11a–f to give the corresponding compounds 12a–f.