Design, synthesis and in vivo/in vitro screening of novel chlorokojic acid derivatives

Mannich bases in medicinal chemistry and drug design

“…Subsequently, a novel series of Mannich bases 125 was synthesized, this time using various 4-(substituted aryl)piperazines as amine reagent, but the compounds in this collection were weaker antibacterials than analogous 125 derived from 4-benzylpiperazines [153]. Screening of another novel set of compounds 125 with either 4benzylpiperazines of 4-arylpiperazines did not identify any compounds with improved or remarkable antibacterial activity, as the best candidates in this study had MIC values between 4 and 16 mg/ mL [154]. However, when piperazinyl-substituted fluoroquinolones were employed as amine reagents in the Mannich reaction of 3hydroxy-4H-pyran-4-ones as substrates, the resulting hybrids 126 (R ¼ Cl) ( Fig.…”

“…Replacement of allomaltol with chlorokojic acid as substrate afforded piperazine Mannich bases 125 (R ¼ 4-substituted piperazin-1-yl) ( Fig. 23), analogous to both 124 and 174 and having comparable antimycobacterial activity (MIC values between 4 and 32 mg/mL), although M. avium rather than M. tuberculosis exhibited the greatest sensitivity towards the candidates 125 [154].…”

“…The authors tentatively explain the enhanced anticonvulsant activity of Mannich bases of kojic acid compared to the activity of Mannich bases of allomaltol through the possible formation of an extra hydrogen bond in the former compounds. However, Mannich bases derived from chlorokojic acid were also good anticonvulsants, and they present, like Mannich bases of allomaltol, only one hydrogen bond in their structure [154].…”

Eco-friendly one-pot, three-component synthesis of novel derivatives of kojic acid by the Mannich-type reaction under solvent-free ball-milling conditions

“…Because of biological activates of Mannich bases, this reaction has attracted increased interest (Compounds II, Fig. 1) [19][20][21][22][23][24]. However, a literature survey shows that most reported articles of Mannich reactions concern the study of kojic acid, To the best of our knowledge, there are no reports on three-component coupling of kojic acid, aromatic aldehydes and heteroaromatic amines to produce a new class of kojic acid derivatives as novel Mannich bases. In recent years, the use of ball-milling (intense mechanical grinding) as an efficient and green tool in organic synthesis has garnered great interest [25][26][27][28][29][30][31][32].…”

A kojic acid derivative promotes intrinsic apoptotic pathway of hepatocellular carcinoma cells without incurring drug resistance

“…In synthesis process, chlorokojic acid (2‐chloromethyl‐5‐hydroxy‐4 H ‐pyran‐4‐one, CKA) was obtained from commercially available kojic acid in a one‐step reaction. 2‐Substituted‐6‐(hydroxymethyl/chloromethyl)‐3‐hydroxy‐4 H ‐pyran‐4‐one (compounds 1 , 2 , 5 and 8 ) derivatives were synthesized with the reaction of appropriate substituted benzylpiperazine derivatives with KA or CKA and formaline at room temperature (Aytemir et al, ; Aytemir, Ozcelik, & Karakaya, ; Karakaya, Aytemir, Ozcelik, & Calis, ; Karakaya et al, ). Finally, Mannich bases of CKA reacted with piperidine or pyrrolidine moieties in the dimethylformamide (DMF) in presence of K 2 CO 3 to synthesize compounds with the structure of 2‐substituted‐3‐hydroxy‐6‐(piperidinylmethyl/pyrrolidinylmethyl)‐4 H ‐pyran‐4‐one (compounds 3 , 4 , 6 , 7 , 9 , and 10) (Karakaya et al, , ).…”