Synthesis and biological activities of new Mannich bases of chlorokojic acid derivatives

Abstract

A novel series of 6-chloromethyl-3-hydroxy-2-substituted 4H-pyran-4-one derivatives were synthesized and tested for their antibacterial, antifungal and antiviral in vitro properties. In the view of activity results, compounds 8-11 (MIC: 8 lg/ml) were more remarkably active against Staphylococcus aureus and Enterococcus faecalis. Compounds 1-7 were highly active against Candida albicans and C. parapsilosis with MIC value of 8 lg/ml. Compound 9 bearing 3-chlorophenyl moiety was determined to be the most active compound against RNA virus PI-3.

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

“…These compounds demonstrated significant anticonvulsant activities in vivo against maximal electroshock (MES)-and subcutaneous pentylenetetrazole (scPTZ)-induced seizure tests. Also, in our recent studies Mannich bases of chlorokojic acid (route B) exhibited good antimicrobial and antiviral activities [10][11] . Therefore in present work we planned to synthesize eighteen novel 6-chloromethyl-3-hydroxy-2-substituted 4H-pyran-4-one derivatives including piperazine ring and evaluate for their anticonvulsant and antimicrobial couplet with antitubercular activities (Scheme 2).…”

“…In our laboratory, a large number of Mannich bases of kojic acid (route A), chlorokojic acid (route B), and allomaltol (route C) were prepared (Scheme 1) for their various types of biological activities 4,[6][7][8][9][10][11] . Most of these compounds seemed to be promising candidates for anticonvulsant, antimicrobial and antiviral agents.…”

“…The mechanisms of this Mannich reaction both in an acidic and a basic medium were investigated and found that, enhanced reactivity in a basic medium is due to increase of the electronegativity at 6-position 42 . It is well known that chlorokojic acid is an important compound from the chemical point of view and as the chlorine atom in the structure readily undergoes nucleophilic substitution 44 , it has been used as starting or intermediate material in many reactions [2][3][4][6][7][8][9][10][11] . General synthesis of compounds is given in Scheme 2.…”

“…General synthesis of compounds is given in Scheme 2. Chlorokojic acid was gained by commercially available kojic acid as described methods from the published literature [8][9][10][11] . In order to obtain chlorokojic acid; 2-hydroxymethyl moiety of kojic acid was chlorinated by using thionyl chloride at room temperature.…”

“…Because of providing a promising skeleton for development of both new and more potent derivatives, it has been used by many researchers as a starting material in preparation of new compounds [1][2][3][4][5][6][7][8][9][10][11] . Chlorokojic acid (2-chloromethyl-5-hydroxy-4H-pyran-4-one), which is synthesized by chlorination of kojic acid exhibits distinct antibacterial and antifungal activities [3][4][5] .…”