Synthesis and evaluation of antitumor activity ofsome thiazolo[4,5-b]pyridines

Abstract

Aim. To synthesize a series of novel 3H-thiazolo[4,5-b]pyridine-2-ones by structural modification of the core heterocycle in its N3- and N6-positions and to evaluate their anticancer activity in vitro on several tumor cell lines. Methods. Organic synthesis, 1H-NMR spectroscopy, trypan blue cell viability assay. Results. A new convenient synthetic approach was developed and optimized conditions were studied for the reaction of preparation of 3H- thiazolo[4,5-b]pyridin-2-one derivatives. 5,7-Dimethyl-3H-thiazolo[4,5-b]pyridin-2-one and 6-phenylazo-5,7- dimethyl-3H-thiazolo[4,5-b]pyridin-2-one were obtained by [3 + 3]cyclocondensation of 4-iminothiazolidone- 2 with acetylacetone and phenylazoacetylacetone in methanol medium in the presence of sodium methylate. They were used as starting compounds for further structural modification of the core thiazolo[4,5-b]pyridine heterocycle in its 3- and 6-positions. On the basis of in vitro cytotoxicity studies of synthesized compounds several structure-functional relationships underlying anticancer potential of 5,7-dimethyl-3H-thiazolo[4,5-b]pyridin- 2-one derivatives were identified. Conclusions. 3H-thiazolo[4,5-b]pyridin-2-one can be considered as a promising molecular scaffold for rational design of potential anticancer drug candidates. Introduction of phenylazo substitute at C6-position of 3H-thiazolo[4,5-b]pyridin-2-one proved to be the most efficient, as it led to 3-fold increase of its anticancer potential

QSAR Studies of Some Thiazolo[4,5-b]pyridines as Novel Antioxidant Agents: Enhancement of Activity by Some Molecular Structure Parameters

“…Previously we reported on the development of synthetic approach to the construction of substituted thiazolo [4,5-b]pyridines based on 4-iminothiazolidine-2 as an initial compound capable of [3+3] cyclocondensation with acetylacetone and α-phenylazoacetylacetone on account of its N,C-binucleophylic properties [8][9][10]. Some biological actions of the novel fused heterocycles like antitumor and antioxidant ones have been also evaluated.…”

ynthesis, Anti-Inflammatory and Antioxidant Activities of Novel 3H-Thiazolo[4,5-b]Pyridines

“…The incorporation of these heterocyclic systems into a bicyclic scaffold commonly provides much more interesting analogs with the enhanced activity profile in comparison with their parent monocyclic constituents. [14][15] Thiazolo [4,5-b] pyridine derivatives are characterized by diverse biological activities, among which antioxidant, [16][17][18] tuberculostatic, 19 anticancer, 20 anti-inflammatory, [21][22] and antifungal 23 effects have been reported in the past decade.…”

Antioxidant properties of some novel derivatives thiazolo[4,5-b] pyridine

“…They also show potent Ab 42 fibrillization inhibitory activities in Alzheimer's disease treatment (Lee et al 2008). Among this type of substances, several compounds were found to possess fungicidal (Marzoog and Al-Thebeiti 1978), anti-inflammatory (Chaban et al 2016(Chaban et al , 2017b(Chaban et al , 2018b(Chaban et al , 2019a, tuberculostatic (Chaban et al 2014), antioxidant (Chaban et al 2013;Klenina et al 2013Klenina et al , 2017 and antitumor effects (Chaban et al 2012a). Some of them are H3 receptor antagonists (Walczyn´ski et al 2005), or act as antagonists of metabotropic glutamate receptors 5 (mGluR5) (Lin et al 2009), they are of high inhibitory activity with respect to the receptors of the epidermal growth factor (Komoriya et al 2006), and were revealed to activate the GK enzyme in vitro and significantly reduces glucose levels (Singh et al 1995).…”