Synthesized successfully 6 4-aza-podophyllotoxin compounds containing heterocycles in the ring E 5a-f via four-component domino reactions (32-50% yields) and three-component domino reactions (64-83% yields).
- Synthesized successfully 17 4-aza-podophyllotoxin compounds 11a-q in 69-89% yields.
- Synthesized successfully 13 N-arylated-dihydrobenzo[g]quinoline-5,10-diones 16a–m in 69-86% yields. 
- Synthesized successfully 8 phenazine--butyrolactone compounds 8’a-h in 62-80% yields. 
- Synthesized successfully 5 compounds 13’a-e in 62 – 75% yields, starting from phenylglyoxal hydrate derivatives. 
- The cytotoxic activity of synthesized compounds was evaluated against cancer cell lines including epidermoid carcinoma (KB), hepatoma carcinoma (HepG2), non-small lung (LU-1 or A549) and breast (MCF7) cancer cell lines. The results showed that 27/44 compounds exhibited cytotoxicity against tested cancer cell lines, of which 16 compounds showed higher cytotoxic activity than those of the reference ellipticine. Besides that, the toxicicty of compounds on non-cancerous human embryonic kidney (Hek-293) cell line was also evaluated. In general, 6 potent compounds 5c, 11h, 11j, 11k, 16i, and 16m exhibited 10 to 200-fold lower cytotoxicity against Hek-293 cell lines than to some tested cancer cell lines. Although compounds 8’a-h didn’t show good cytotoxicity, they exhibited potential anti-inflammatory activity by inhibiting NO production.
- The initial findings have indicated the anticancer mechanism of 4-aza-podophyllotoxin compounds 11j and 11k by arresting the G2/M phase of the cell cycle, activating caspase-3/7 enzymes, and inducing apoptosis. Additionally, the tubulin inhibition mechanism of these two compounds has also been proposed through molecular docking simulations.

The project focused on the synthesis of 4-aza-podophyllotoxin derivatives by using multicomponent reactions. The synthesized compounds were evaluated anti-cancer activities by using MTT method (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazoliumbromid) to assess their cytotoxicity against KB, HepG2, A549 (or LU-1), MCF7 cancer cell lines. The results indicated that several compounds exhibited potential cytotoxicity against tested cancer cell lines. Notably, some compounds displayed higher cytotoxicity than ellipticine  as a reference. Two compounds 11j, and 11k exhibited the most potential activity against LU-1 cells (IC50 < 50 nM) were further studied for their anti-cancer activity using flow cytometry and  molecular docking. The most potent cytotoxic compounds 11j, and 11k were found to possess anti-proliferative activity through concentration-dependently inducing cell cycle arrest at G2/M phase, caspase-3/7 activation, and apoptosis as well. Moreover, molecular docking studies exhibited importance interaction of two compounds against residues in the colchicine-binding-site of tubulin. These preliminary results revealed that podophyllotoxin-naphthoquinone compounds are worthy of further study aiming to develop new potential anticancer agents.
Besides that, the projetct also studied on the synthesis and biological evaluation of phenazine--butyrolactone compounds 8’a-h. Those compounds, which were synthesized by using “one-pot” two-step four-component reactions, exhibited potential anti-inflammatory activity by inhibiting NO production.  Their inhibitory activity was higher than that of L-NG-monomethyl arginine citrate (L-NMMA) as a reference.  Therefore, compounds 8’a-h have potential of further development of anti-inflammatory agents due to their inhibitory effects on NO production. Moreover, several epidemiological studies have demonstrated that inflammation can predispose to tumors, therefore, due to  anti-inflammatory effects of compounds 8’a-h, these compounds may have great potential in cancer prevention and therapy.