Abstract
One of the promising methods of creating antitumor drugs is the screening of potential antitumor agents among synthesized compounds. Nitrogen-based heterocycle analogues are an extremely important class of organic substances that are widely used in medical chemistry. [1,2,4]Triazolo[3,4-b][1,3,4] thiadiazoles are among the little-studied and hard-to-reach members of this class of compounds.
 The aim of our work was to synthesize some new 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles, as well as the study of their antitumor activity.
 The objects of study were 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles. The composition and structure of the synthesized compounds were confirmed by the data of elemental analysis and 1H NMR spectroscopy. The antitumor activity of the synthesized compounds was studied in the framework of the international scientific program of the National Cancer Institute (Bethesda, Maryland, USA) DTP NCI (Developmental Therapeutic Program).
 The synthesis of 11 derivatives of 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles was carried out. These substances are obtained by the interaction of 5-arylfuran-2-carboxylic acids with 5-substituted 4-amino-4H-1,2,4-triazolo-3-thiols. Primary screening revealed individual 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles, which showed pronounced selective antitumor activity. The most active among the tested compounds were 3 d, 3 e and 3 j, which were further investigated during secondary screening. The results of these studies confirm the high antitumor activity of these compounds.
 The proposed approaches and the developed synthesis protocols made it possible to obtain a series of new 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles. The results of studies of the antitumor activity of the synthesized compounds made it possible to single out 3 highly active compounds with high antitumor activity, which gives reason to consider this condensed system as a promising molecular framework for the design of potential antitumor agents.
Highlights
Онкологічні захворювання є однією з найнебезпечніших медико-біологічних та соціальних проблем сьогодення і є причиною до 12% усіх випадків смерті та поступаються за цим показником лише серцево-судинним захворюванням [1]
Більшість отриманих сполук не знаходять клінічного застосування через свою високу токсичність, погану розчинність у воді, невибіркову дію та низку інших побічних ефектів [2]
Кінцеву точку визначали за допомогою барвника – сульфородаміну Б
Summary
Метою нашої роботи став синтез деяких нових похідних 3-R-6-(5-арилфуран-2іл-[1,2,4]триазоло[3,4-b][1,3,4]тіадіазолу, а також дослідження їхньої протипухлинної активності. Протипухлинна активність синтезованих сполук вивчена в рамках міжнародної наукової програми Національного інституту раку (Бетезда, Меріленд, США) DTP NCI (Developmental Therapeutic Program) [20] і полягала в тестуванні на 60 лініях ракових клітин, зокрема лейкемії (Leukemia) (CCRF-CEM, HL-60(TB), K-562, MOLT-4, RPMI-8226), недрібноклітинного раку легень (Non-Small Cell Lung Cancer) (A549/ATCC, EKVX, HOP62, HOP-92, NCI-H226, NCI-H23, NCI-H322M, NCI-H460, NCI-H522), раку товстої кишки (Colon Cancer) (COLO 205, HCС-2998, HCT-116, HCT-15, HT29, KM12, SW620), раку ЦНС (CNS Cancer) (SF-268, SF-295, SF-539, SNB-19, SNB-75, U251), меланоми (Melanoma) (LOX IMVI, MALME-3M, М14, MDA-MB-435, SK-MEL-2, SKMEL-28, SK-MEL-5, UACC-257, UACC-62), раку яєчників (Ovarian Cancer) (IGROV1, OVCAR-3, OVCAR-4, OVCAR-5, OVCAR-8, NCI/ADR-RES, SK-OV-3), раку нирок (Renal Cancer) (786-0, A498, ACHN, CAKI-1, RXF 393, SN12C, TK-10, UO-31), раку простати (Prostate Cancer) (PC-3, DU-145) та раку молочної залози (Breast Cancer) (MCF7, MDA-MB-231/ATCC, HS 578T, BT-549, T-47D, MDA-MB-468). In vitro дослідження протипухлинної активності сполук 3 d, 3 e та 3 j на 60 лініях ракових клітин за градієнта концентрацій (10-4–10-8М)
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