Synthesis and Biological Evaluation of Amidine, Guanidine, and Thiourea Derivatives of 2-Amino(6-trifluoromethoxy)benzothiazole as Neuroprotective Agents Potentially Useful in Brain Diseases

Abstract

A series of amidine, thiourea, and guanidine derivatives of 2-amino-6-(trifluoromethoxy)benzothiazole termed 2, 3, and 4, respectively, and structurally related to riluzole, a neuroprotective drug in many animal models of brain disease, have been synthesized. The biological activity of compounds 2a-e, 3a-f, and 4a,b was preliminarily tested by means of an in vitro protocol of ischemia/reperfusion injury. The results demonstrated that 2c and 3a-d significantly attenuated neuronal injury. Selected for testing of their antioxidant properties, compounds 3a-d were shown to be endowed with a direct ROS scavenging activity. Compounds 3b and 3d were also evaluated for their activity on voltage-dependent Na(+) and Ca(2+) currents in neurons from rat piriform cortex. At 50 microM, compound 3b inhibited the transient Na(+) current to a much smaller extent than riluzole, whereas 3d was almost completely ineffective.

Synthesis, characterization and carbonic anhydrase inhibitory activity of novel benzothiazole derivatives

“…New N-protected amino acid benzothiazole conjugates (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) were synthesized by the treatment of appropriate benzothiazole derivatives and N-protected amino acid (Gly, Ala and Phe) derivatives under microwave heating at 70 C for 45 min with good yields of 60-70%. The compound 13 was synthesized from the reacting of (S)-tert-butyl (1-( (4- As it is seen in Table 1 none of the N-protected amino acidbenzothiazole conjugates 1-13 showed affinity toward to membrane-associated isoform hCA IV and compounds 12 and 13 are inactive on four hCAs tested in this study.…”

“…Among them, benzothiazoles, in particular, have been studied extensively because of their biological activities as antitumor 2 , anti-inflammatory 3 , antimicrobial 4 , anticonvulsant 5 , neuroprotective 6 , kinase 7 , microsomal triglyceride transfer protein 8 and carbonic anhydrase inhibitors (CAIs) 9 . On the other hand, short peptides and their conjugates exhibit a broad spectrum of biological activity.…”

N-Adamantyl-4-Methylthiazol-2-Amine Attenuates Glutamate-Induced Oxidative Stress and Inflammation in the Brain

“…To develop effective agents against glutamate-induced toxicity, we have screened novel thiazole derivatives because of their therapeutic potential as anti-inflammatory and antioxidative agents and as candidate drugs for the regulation of glutamate transmission by increasing glutamate uptake and affinity for its transporters (Fumagalli et al 2008;Gribkoff and Bozik 2008;Anzini et al 2010;Gallardo-Godoy et al 2011;Geronikaki et al 2013;Li et al 2013;El-Achkar et al 2015). For instance, thiazol-2-amine derivatives showed desirable properties as improved lead compounds for the treatment of brain disease, including ROS-scavenging activity, good stability in liver microsomes, oral bioavailability as a metabotropic glutamate receptor 1 antagonist, and high exposure in the brains of mice (Gribkoff and Bozik 2008;Satoh et al 2009;Anzini et al 2010;Gallardo-Godoy et al 2011;Li et al 2013).…”

Synthesis, anti‐inflammatory, and anticancer activity evaluation of some heterocyclic amidine and bis‐amidine derivatives

“…These structural motifs possess wide variety of biological activities such as anti-inflammatory [1][2][3][4], anticancer [5][6][7][8], antimicrobial [9], antibacterial [10], and antifungal [11]. Riluzole drug, which is a derivative of benzothiazole, is useful in the treatment of brain diseases and prostate cancer [12]. Amidino-benzimidazole derivatives exhibit anticancer activity by targeting the minor groove of DNA [13].…”