2-(Dichloromethyl)pyrazolo[1,5-a][1,3,5]triazines: synthesis and anticancer activity

Abstract

Synthesis of a series of 2-(dichloromethyl)pyrazolo [1,5-a][1,3,5]triazines and evaluation in vitro of their anticancer activity against a panel of 60 cell lines derived from nine cancer types, namely leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer, breast cancer. Methods. Organic synthesis; biological tests; spectral methods; statistical methods. Results. In vitro screening of the anticancer activity showed that 5 of 26 tested compounds can effectively inhibit the growth of certain cancer cell lines. Conclusions. New type of N-(2,2-dichloro-1-cyanoethenyl)carboxamides heterocyclization with 1H-pyrazol-5-amines led to the formation of 2-(dichloromethyl)pyrazolo [1,5-a][1,3,5]triazines. Some of these compounds inhibit growth of certain cancer cell lines.

Recent Advances in the Biological Activity of s-Triazine Core Compounds

“…Moreover MCF-7 cells were significantly arrested in the G2/M stage. An in vivo studies of 34 in zebrafish presented non-toxic properties [36].…”

“…Screening studies of 2-(dichloromethyl)pyrazolo[1,5-a][1,3,5]triazines 62-66 (Figure 13) showed potential anticancer properties against non-small cell lung cancers, colon cancers, renal cancer, etc. [36]. Screening studies of 2-(dichloromethyl)pyrazolo[1,5-a][1,3,5]triazines 62-66 (Figure 13) showed potential anticancer properties against non-small cell lung cancers, colon cancers, renal cancer, etc.…”

Functionalized 5‐Amino‐4‐cyanoxazoles, their Hetero‐ and Macrocyclic Derivatives: Preparation and Synthetic Applications

“…This reagent was introduced into the chemistry of heterocyclic compounds in 1970s. [28,29] Recent publications report the use of 5 for the preparation of imidazol-2-ones, [30] pyrazolo- [1,5-a] pyrimidines, [31] pyrazolo [1,5-a] [1,3,5]triazines, [32] as well as a number of trisubstituted oxazoles. [33][34][35] The latter approach includes acylation of 5 at the amino group with acyl halides or anhydrides, followed by reaction with a primary or secondary aliphatic, or primary aromatic amine, resulting in the formation of the oxazole ring (Scheme 1E).…”

Spectroscopic studies, quantum chemical investigations, and in silico and in vitro scrutiny of the diuretic drug trichlormethiazide adsorbed onAuNPs

“…This challenge paved the way toward the search for new promising lung cancer therapeutic agents. It has been identified that the derivatives of sulfonamide (electronegative group), benzothiadiazine (fused ring), and dichloromethyl (electronegative group) have multifarious pharmacological activities and have potential applications in the field of medicine 4–8 . In addition, sulfonamides are identified as the first major drug to be used, and they form an integral component of more than 30 drugs used in the clinical field; 9–23 Dichloromethyl groups have been reported to show significant antiviral activity 7,8 .…”

“…It has been identified that the derivatives of sulfonamide (electronegative group), benzothiadiazine (fused ring), and dichloromethyl (electronegative group) have multifarious pharmacological activities and have potential applications in the field of medicine 4–8 . In addition, sulfonamides are identified as the first major drug to be used, and they form an integral component of more than 30 drugs used in the clinical field; 9–23 Dichloromethyl groups have been reported to show significant antiviral activity 7,8 . The efficacies of benzothiadiazines in clinical applications such as schizophrenia, depression, Alzheimer's disease, Parkinson's disease, ADHD, and respiratory depression have also been recognized 24–33 …”