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Due to the importance of biological activities of 1,2,4-triazine derivatives, in this manuscript, ten of newly synthesized compounds containing 1,2,4-triazine moiety were prepared. Anticancer and antimicrobial activities of some selected synthesized compounds were screened. Chalcone derivatives 6, 7 were synthesized via reaction of Mannich base 2 in acetic acid and fused sodium acetate with formyl khellin 5 or vanillin. Treatment of chalcone derivatives 6, 7 toward hydrazine hydrate, phenyl hydrazine, hydroxylamine hydrochloride or malononitrile, respectively, led to give pyrazoline 8, 9, 10, 11, oxazole 12, 13 and pyridine 14, 15 derivatives, respectively. The structures of the isolated products were established by elementary analysis and spectral data studies. Compounds 1, 5, 6, 8, 10, 12 and 14 were tested against different human cancer cell lines, and cytotoxicity in vitro and most of the synthesized compounds were proved to have high activities against cytotoxic test. Then, the compounds 1, 5, 6, 8, 10, 12 and 14 were tested against cancer in vivo, and the result was established. Also, antimicrobial activity of compounds 1, 5, 6, 8, 10, 12 and 14 was screened in vitro against a panel of gram-positive and gram-negative bacterial pathogens and fungi. The results indicated that compound 5 showed higher antimicrobial activity than compounds 1, 6, 8, 10, 12 and 14, and compound 5 exhibited a wide range of antimicrobial activities against gram-positive and gramnegative bacteria and fungi, greater than well-known antibacterial and antifungal agents with minimal inhibitory concentration ranged between 6.25 and 25 lg.

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Cancer is a complex and heterogeneous disease and is still one of the leading causes of morbidity and mortality worldwide, mostly as the population ages. Despite the encouraging advances made over the years in chemotherapy, the development of new compounds for cancer treatments is an urgent priority. In recent years, the design and chemical synthesis of several innovative hybrid molecules, which bring different pharmacophores on the same scaffold, have attracted the interest of many researchers. Following this strategy, we designed and synthetized a series of new hybrid compounds that contain three pharmacophores, namely trimethoxybenzene, thiazolidinedione and thiazole, and tested their anticancer properties on two breast cancer (MCF-7 and MDA-MB-231) cell lines and one melanoma (A2058) cell line. The most active compounds were particularly effective against the MCF-7 cells and did not affect the viability of the normal MCF-10A cells. Docking simulations indicated the human Topoisomerases I and II (hTopos I and II) as possible targets of these compounds, the inhibitory activity of which was demonstrated by the mean of direct enzymatic assays. Particularly, compound 7e was proved to inhibit both the hTopo I and II, whereas compounds 7c,d blocked only the hTopo II. Finally, compound 7e was responsible for MCF-7 cell death by apoptosis. The reported results are promising for the further design and synthesis of other analogues potentially active as anticancer tools.