| Abstract [eng] |
The discovery of new biologically active molecules is one of the key elements of medicinal chemistry. Fragments of compound known to possess biological activity and their combinations can be used to obtain new molecules with better biological properties. Pyrazole derivatives have a wide range of applications as medicinal products due to their antimicrobial, anticancer and antiviral properties. Flavanone derivatives are widespread in nature, their effects on living organisms are also diverse - antioxidant, anti-inflammatory, antihypertensive. The aim of this work was to synthesize new 2-(3-alkyloxy-1-phenyl-1H-pyrazol-4-yl)chroman-4-one derivatives starting from 1-phenyl-1H-pyrazol-3-ol with pyrazole and flavonone fragments, to determine suitable synthesis method and to investigate the biological effects of the synthesized derivatives. First, for the preparation of pyrazole-flavanone derivatives - (3-alkyloxy-1-phenyl-1H-pyrazol-4-yl) chroman-4-ones, the intermediate 3-alkyloxy-1-phenyl-1H-pyrazole-4-carbaldehydes were obtained in two steps synthesis employing alkylation and formylation reactions. Targeted (3-alkyloxy-1-phenyl-1H-pyrazol-4-yl)chroman-4-ones were synthesized from O-pyrazolecarbaldehydes by several single-step methods: a combination of the Claisen-Schmidt condensation reaction and the Michael addition reaction, and the Manich β-transformation reaction of aminocarbonyl products. The Manich reaction was found to be most convenient to obtain the target cyclic compounds. After optimizing the reaction conditions, a series of (3-alkyloxy-1-phenyl-1H-pyrazol-4-yl)chroman-4-one derivatives was obtained from the substituted 2-hydroxyacetophenones and the corresponding O-pyrazole-4-carbaldehydes by a one-pot reaction. Analysis of biological activity investigation results of the targeted compounds have shown that (3-alkyloxy-1-phenyl-1H-pyrazol-4-yl)chroman-4-ones have low anticancer activity, although several compounds could be further investigated. Antibacterial studies of the compounds have also shown the activity of several derivatives in inhibiting the growth of gram-negative bacteria. The structures of the obtained compounds were confirmed by spectroscopic and spectrometric methods. Anticancer activity studies were performed by Vladimír Kryštof’s group (Palacký University, Olomouc, Czech Republic), antibacterial studies were performed in Kaunas University of Technology Biotechnology Laboratory by agar diffusion method. |
