Development and therapeutic potential of 2-aminothiazole derivatives in anticancer drug discovery

Abstract

Currently, the development of anticancer drug resistance is significantly restricted the clinical efficacy of the most commonly prescribed anticancer drug. Malignant disease is widely prevalent and considered to be the major challenges of this century, which concerns the medical community all over the world. Consequently, investigating small molecule antitumor agents, which could decrease drug resistance and reduce unpleasant side effect is more desirable. 2-aminothiazole scaffold has emerged as a promising scaffold in medicinal chemistry and drug discovery research. This nucleus is a fundamental part of some clinically applied anticancer drugs such as dasatinib and alpelisib. Literature survey documented that different 2-aminothiazole analogs exhibited their potent and selective nanomolar inhibitory activity against a wide range of human cancerous cell lines such as breast, leukemia, lung, colon, CNS, melanoma, ovarian, renal, and prostate. In this paper, we have reviewed the progresses and structural modification of 2-aminothiazole to pursuit potent anticancers and also highlighted in vitro activities and in silico studies. The information will useful for future innovation. Representatives of 2-aminothiazole-containing compounds classification.

Keywords: 2-aminothiazole; Alpelisib; Anticancer; Dasatinib; Hantzsch’s synthesis; SAR study.

Representatives of 2-aminothiazole-containing compounds classification

Fig. 1

Development of 2-aminothiazole core in anticancer therapeutic areas

Fig. 2

General reaction for Hantzsch’s synthesis of 2-aminothiazole

Fig. 3

Various synthetic routes to the 2-aminothiazole core preparation

Fig. 4

2-Aminothiazole scaffold containing amide moiety (7-14)

Fig. 5

2-Aminothiazole scaffold containing amide moiety (15-22)

Fig. 6

2-Aminothiazole scaffold containing amide moiety (23-34)

Fig. 7

Analogs of girollines; a natural antitumor agent

Fig. 8

2-Aminothiazole scaffold containing urea and thiourea moiety (37–44)

Fig. 9

2-Aminothiazole scaffold containing alkyl moiety (45-50)

Fig. 10

2-Aminothiazole scaffold containing alkyl Moiety (51-58)

Fig. 11

Design 2-aminothiazoles as microtubule targeting agents based on combretastatin

Fig. 12

Design 2-aminothiazoles as chalcone-like anticancer agents

Fig. 13

Oridonin analogues with 2-aminothiazole-fused A-ring

Fig. 14

Modifications of the known SKI-II scaffold to an aminothiazole class of SphK inhibitors

Fig. 15

2-Aminothiazole scaffold containing aryl Moiety (70-75)

Fig. 16

2-Aminothiazole scaffold containing aryl moiety (76- 84)

Fig. 17

2-Aminothiazole scaffold containing pyridine moiety (85-87)

Fig. 18

2-Aminothiazole scaffold containing pyrimidine moiety

Fig. 19

Hybridization of dasatinib and MS-275 pharmacophores

Fig. 20

Schiff base containing 2-aminothiazole moiety

Fig. 21

2-Aminothiazole scaffold containing hydrazone moiety (99-102)

Fig. 22

2-Aminothiazole scaffold containing sulfonamide moiety for treating gastrointestinal adenocarcinoma