Synthesis of New 6-{[ω-(Dialkylamino(heterocyclyl)alkyl]thio}-3-R-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones and Evaluation of their Anticancer and Antimicrobial Activities

Abstract

Several novel 6-thio-3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-based compounds containing an ω-(dialkylamino(heterocyclyl)]alkyl fragment were synthesized to examine their anticancer activity. Some of the 6-{[ω-(hetero-cyclyl)alkyl]thio}-3-R-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones (3.1–3.10) were obtained by the nucleophilic substitution of 6-[ω-halogenalkyl]thio-3-R-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones (2.1–2.8) with azaheterocycles. Alternatively, compounds 3.1–3.22 were synthesized by alkylation of 3-R-6-thio-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones potassium salts (1.1–1.4) with (2-chloroethyl)-N,N-dialkylamine hydrochlorides or 1-(2-chloroethyl)heterocycle hydrochlorides. The structures of compounds were elucidated by 1H, 13C NMR, LC–MS and EI-MS analysis. Then anticancer and antibacterial, bioluminescence inhibition of Photobacterium leiognathi Sh1 activities of the substances were tested in vitro. It was found that compound 3.18 possessed a wide range of anticancer activity against 27 cell lines of cancer: non-small cell lung, colon, CNS, ovarian, renal, prostate, breast, melanoma and leukemia (log GI50 < −5.65). The “structure-activity” relationship was discussed. COMPARE analysis for synthesized anticancer active compounds was performed.

Physico-chemical Properties, Biological and Environmental Impact of Nb-saponites Catalysts for the Oxidative Degradation of Chemical Warfare Agents

“…The impact of the saponites on the biological and environmental activity of bioluminescent bacteria and vegetables was assessed by means of specific biotoxicity tests. Native marine luminescent bacteria are, in fact, widely used as a biotest to study toxicity of chemicals, waste waters and eluates from soil and sediments. Such assays are based on the quantitative study of bioluminescence inhibition as a function of the amount of contaminant species .…”

Peculiarites of interaction between 3-(2-aminophenyl)-6-R-1,2,4-triazin-5(2H)-ones and cyclic anhydrides of non-symmetric dicarboxylic acids

“…Проведено обсуждение влияния электронных и стерических эффектов заместителей на процессы циклизации. Результаты показали, что взаимодействие приведенных выше 3-(2-аминофенил)-6-R-1,2,4триазин-5(2H)-онов с ангидридами 2-метилянтарной и 2-фенилянтарной кислот протекало не региоселективно с образованием смесей 2-R 1 -3-(2-оксо-3-R-2H- [1,2,4]триазино [2,3-c]хиназолин-6-ил)пропановых кислот и 1-(2-(5-оксо-6-R-2,5-дигидро-1,2,4триазин-3-ил)фенил)-3-R 1 -пиролидин-2,5-дионов. Показано, что низкая региоселективность процесса ацилирования может быть объяснена незначительными электронными эффектами заместителей (метильного и фенильного фрагмента) в положении 2 молекулы ангидрида на электрофильный реакционный центр.…”

Synthesis and Antimicrobial Activity of 6-Thioxo-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]quinazolin-2-one Derivatives

“…Recent publications describe the synthesis and biological activity of the [ 1 , 2 , 4 ]triazino[ 2 , 3 - c ]-quinazoline series [ 5 – 13 ]. It is known that the introduction of a thio-group in position 6 of the [ 1 , 2 , 4 ]triazino[ 2 , 3 - c ]quinazoline system allows the obtainment of compounds with significant cytotoxic action against Photobacterium leiognathi [ 9 , 11 – 13 ] and antimicrobial action against Staphyloccocus aureus and Aspergillus niger [ 8 – 13 ]. The following structure modification of 6-thio-3-R-2 H -[ 1 , 2 , 4 ]triazino[ 2 , 3 - c ]quinazoline-2-ones by synthesis of S-substituted derivatives enabled the obtainment of compounds with anticancer action [ 9 , – 13 ].…”