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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.

Berest GG, Voskoboynik OY, Kovalenko SI, Nosulenko IS, Antypenko LM, Antypenko OM, Shvets VM, Katsev AM - Sci Pharm (2011)

Bottom Line: The structures of compounds were elucidated by (1)H, (13)C NMR, LC-MS and EI-MS analysis.The "structure-activity" relationship was discussed.COMPARE analysis for synthesized anticancer active compounds was performed.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Zaporozhye State Medical University, Mayakovsky ave., 26, 69035, Zaporozhye, Ukraine.

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 (1)H, (13)C 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 GI(50) < -5.65). The "structure-activity" relationship was discussed. COMPARE analysis for synthesized anticancer active compounds was performed.

No MeSH data available.


Related in: MedlinePlus

Synthesis of the 6-{[2-(heterocyclyl)ethyl]thio}-3-R-2H-[1,2,4]triazino[2,3-c]quinazoline-2-one (3.1–3.3) and 6-{[2-(dialkylamino)ethyl]thio}-3-R-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones (3.11–3.22).
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f4-scipharm.2012.80.37: Synthesis of the 6-{[2-(heterocyclyl)ethyl]thio}-3-R-2H-[1,2,4]triazino[2,3-c]quinazoline-2-one (3.1–3.3) and 6-{[2-(dialkylamino)ethyl]thio}-3-R-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones (3.11–3.22).

Mentions: The 3-R-6-thio-6,7dihydro-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones (1.1–1.4) potassium salts were alkylated with (2-chloroethyl)-N,N-dialkylamines hydrochlorides or 1-(2-chloro-ethyl)heterocycles hydrochlorides in the presence of triethylamine to fulfill the second approach (Scheme 3). The water–propan-2-ol reaction medium provided the higher yields of resulting products 3.1–3.3, 3.11–3.22.


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.

Berest GG, Voskoboynik OY, Kovalenko SI, Nosulenko IS, Antypenko LM, Antypenko OM, Shvets VM, Katsev AM - Sci Pharm (2011)

Synthesis of the 6-{[2-(heterocyclyl)ethyl]thio}-3-R-2H-[1,2,4]triazino[2,3-c]quinazoline-2-one (3.1–3.3) and 6-{[2-(dialkylamino)ethyl]thio}-3-R-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones (3.11–3.22).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3293349&req=5

f4-scipharm.2012.80.37: Synthesis of the 6-{[2-(heterocyclyl)ethyl]thio}-3-R-2H-[1,2,4]triazino[2,3-c]quinazoline-2-one (3.1–3.3) and 6-{[2-(dialkylamino)ethyl]thio}-3-R-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones (3.11–3.22).
Mentions: The 3-R-6-thio-6,7dihydro-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones (1.1–1.4) potassium salts were alkylated with (2-chloroethyl)-N,N-dialkylamines hydrochlorides or 1-(2-chloro-ethyl)heterocycles hydrochlorides in the presence of triethylamine to fulfill the second approach (Scheme 3). The water–propan-2-ol reaction medium provided the higher yields of resulting products 3.1–3.3, 3.11–3.22.

Bottom Line: The structures of compounds were elucidated by (1)H, (13)C NMR, LC-MS and EI-MS analysis.The "structure-activity" relationship was discussed.COMPARE analysis for synthesized anticancer active compounds was performed.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Zaporozhye State Medical University, Mayakovsky ave., 26, 69035, Zaporozhye, Ukraine.

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 (1)H, (13)C 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 GI(50) < -5.65). The "structure-activity" relationship was discussed. COMPARE analysis for synthesized anticancer active compounds was performed.

No MeSH data available.


Related in: MedlinePlus