Synthesis, Cytotoxicity by Bioluminescence Inhibition, Antibacterial and Antifungal Activity of ([1,2,4]Triazolo[1,5‐c]quinazolin‐2‐ylthio)carboxylic Acid Amides

Abstract

We report in this work the synthesis, cytotoxicity, and antimicrobial activity of ([1,2,4]triazolo[1,5-c]quinazolin-2-ylthio)carboxylic acid amides 4-7 in connection with our previous research in the preparation of triazoloquinazoline derivatives. Due to simplicity, general availability of starting materials, and high yields, the most reliable method of synthesis appeared to be the one with N,N-carbonyldiimidazole activation stage. The chemical structures of all obtained substances were deduced from FT-IR, (1)H-NMR, EI-MS, and LC-MS spectral data. The results of cytotoxicity evaluated by bioluminescence inhibition of bacterium Photobacterium leiognathi, strain Sh1 showed that compounds 4.1, 4.6, and 6.1 were the most cytotoxic. Investigation of the antimicrobial and antifungal activity of amides 4-7 (concentration 5 mg/mL) was carried out by the stiff-plate agar-diffusion method. We found that the compounds possessed low (4.1, 4.7) antifungal activity against Candida tenuis and strong (4.21, 5.1, 5.9) or inefficient (4.7, 4.12, 4.16) activity against Aspergillus niger. Substances 5.1 and 5.9 slightly affected Mycobacterium luteum. Staphylococcus aureus was resistant to all obtained substances, and only the n-butyramide derivatives 7.1 and 7.5 inhibited the growth of Escherichia coli. Hence, there was no strong correlation between bioluminescence inhibition and antimicrobial activity of the investigated substances.

Design and Evaluation of Novel Antimicrobial and Anticancer Agents Among Tetrazolo[1,5-c]quinazoline-5-thione S-Derivatives

“…Moreover, our previous investigations in the series of similar condensed heterocycles, namely, 2-thio-[1,2,4]triazolo[1,5- c ]quinazoline derivatives, showed that ([1,2,4]triazolo[1,5- c ]quinazolin-2-ylthio)carboxylic acids and amides ( 3 ) possessed antifungal activity against Candida albicans and Aspergillus niger [26, 27]. So, the aim of this work is the purposeful formation of the tetrazolo[1,5- c ]quinazoline-5-thione skeleton, synthesis of its S-derivatives, and screening of their antibacterial, antifungal, and antitumor properties with subsequent docking studies of the most active ones.…”

2‐Heteroaryl‐[1,2,4]triazolo[1,5‐c]quinazoline‐5(6 H)‐thiones and Their S‐Substituted Derivatives: Synthesis, Spectroscopic Data, and Biological Activity

“…In addition, compounds 3 were characterized by the functional substituent signals at position 2, which, depending on the structure, had classical magnetic shifts and the corresponding multiplicity. [15][16][17][18] In the spectra of compounds 6 and 7, the triazoloquinazoline fragment of molecules formed a characteristic subspectrum of two one-proton doublets: H-10 at d = 8.48-8.35 ppm and H-7 at d = 7.97-7.83 ppm, and two one-proton triplets: H-8 at d = 7.85-7.60 ppm and H-9 at d = 7.67-7.60 ppm. The data indicated that the chemical shifts of these protons differed from those of the parent compounds 3 and, as expected, they significantly affected the nature of the substituent at position 5.…”

“…[5,[15][16][17][18] Other starting materials and solvents were obtained from commercially available sources and used without additional purification.…”

Substituted 2-[(2-Oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)thio]acetamides with Thiazole and Thiadiazole Fragments: Synthesis, Physicochemical Properties, Cytotoxicity, and Anticancer Activity

“…The marine luminescent bacteria Photobacterium leiognathi strain Sh1, isolated from the Azov Sea Shrimp, were used for the bioluminescence analysis [25, 26]. Bacteria were cultivated on a nutrient environment containing (g/L): pepton – 5, yeast extract – 1.5, meat extract – 1.5, sodium chloride – 30, pH = 7.4.…”