Zsuzsanna Rozmer

Naturally occurring chalcones and their biological activities

The aim of this review is to summarize the various naturally occurring chalcone compounds which have been isolated from different plants. Chalcones considered as obligate intermediated in flavonoid biosynthesis but they do not accumulate to appreciable degree in most plants. The largest number of natural chalcones has been isolated from species of the Leguminosae, Asteraceae and Moraceae families. Chalcone accumulating plants have often been used in traditional medicine and chalcones have therefore been studied and reported to possess many beneficial biological effects including anti-inflammatory, antimicrobial, antifungal, antioxidant, cytotoxic, antitumor and chemopreventive activities. Previously published reviews on this topic survey the biological activities of natural and synthetic chalcones but there are no comprehensive contributions on occurrence and biological activities of natural chalcones. The present study provides an overview of hydroxy or/and methoxy-substituted chalcones, methylated, prenylated, geranylated and other monomeric derivatives, chromeno- and furanochalcones, dimeric chalcones and dihydrochalcone derivatives focusing on their biosynthesis, natural sources and biological activities. On the basis of 608 references, this review covers the phytochemistry and biological activity of natural chalcones, describing 646 compounds have been appeared in the literature since 1975. The summary is aimed to initiate further pharmacobotanical, biotechnological and medicinal studies on the field of chalcone research.Graphical AbstractThis contribution reviews some of the general aspects of naturally occurring chalcones including their chemical categories, focusing on plant sources and biological activities. The review covers the major works appeared in the literature from 1975 up to 2014, relating to 608 references and 646 compounds.

Kinetic analysis of some chalcones and synthetic chalcone analogues on the fenton-reaction initiated deoxyribose degradation assay.

Investigation of in vitro hydroxyl radical scavenging (antioxidant) effect 4-methoxychalcone (1a) and its cyclic analogues (2a-4a), as well as their hydroxyl substituted counterparts (1b-4b) was performed by means of the Fenton-reaction initiated deoxyribose degradation assay in short term (10 minute) and long term (240 minute) experiments. The kinetic deoxyribose method provides possibility to investigate not only the short term antioxidant (hydroxyl radical scavenger) effect but the possible late prooxidant effect of the tested substances as well. In the short term studies compounds 2a, 2b and 4b showed the most pronounced antioxidant effect. The long-term studies showed that the antioxidant activity of all the tested compounds but 4a can be well characterized by the short time determination of the thiobarbituric acid (TBA)-reactive substances (TBARS). Experiments in the presence of ethylenediaminetetraacetic acid (EDTA) resulted in a substantially reduced degradation of deoxyribose in each incubation. Similar to the respective experiment performed without EDTA, the TBARS level of the incubations with 4a showed an increase over the 60-120 minute period. The results demonstrated that complex forming activities that can modify microspeciation and reactivity of iron ions can lead to different short term antioxidant efficiency of the tested substances. Results of the long term incubations indicated that chemical transformation of the tested substances can result formation of derivatives that can initiate further redox activities under the experimental conditions.

Use of RP-TLC for Determination of log P of Isomeric Chalcones and Cyclic Chalcone Analogues

log P values of 29 biologically active chalcone (1) and cyclic chalcone analogues E-2-(X-benzylidene)-l-indanones (2) and E-2-(X-benzylidene)-1-tetralones (3) have been determined by an optimized and validated RP-TLC method. RP-TLC was performed on silanized silica gel 60F254 as stationary phase with methanol-water, 60 + 40 (v/v) as mobile phase. The RP-TLC method was validated by analysis of three drugs, diazepam, progesterone, and PGE1 ethyl ester, with known log PSF (shake-flask) values. The experimentally determined log PTLC values were compared with the log P values predicted by use of the CLOGP program. On the basis of the log PTLC values of the investigated chalcones (1), the cyclic chalcone analogues (2, 3), and previously investigated, related, E-2-(X-ben-zylidene)-1-benzosuberones (4) the effect on lipophilicity of ring size and the nature and position of substituents were studied. It was found that the open-chain chalcones (1) and the five-membered ring E-2-(X-benzylidene)-1-indanones (2) have similar lipophilicity. Changing the ring size from five to six (3) and from six (3) to seven (7) resulted in the expected increase of the log P values of the compounds. The results indicate importance of steric and electronic factors in the lipophilicity of the compounds investigated.

Comparison of structure, logP and P388 cytotoxicity of some phenyl and ferrocenyl cyclic chalcone analogues. Application of RP-TLC for logP determination of the ferrocenyl analogues

AbstractCyclic chalcone analogues (2–5) and their ferrocenyl counterparts (6–10) were synthesized and their logP and P388 cyctotoxity were investigated. The structures of the newly synthesized compounds were confirmed by IR 1H and 13NMR spectroscopy. Comparison of conjugation and stereochemistry of the respective derivatives showed similar characteristics compared to ones with some higher degree of conjugation in the ferrocenyl series. Comparison of logP of the ferrocenyl derivatives determined by a validated RP-TLC method showed the ferrocenyl derivatives to have higher logPTLC. The results demonstrate that the differences in three dimensional shape, conjugation and lipophilicity do not have strong influence on the P388 cytotoxicity of the investigated phenyl (1−5) and ferrocenyl (6−10) enones.

(E)-2-Benzylidenecyclanones: part XIV. Study on interaction of some (E)-2-benzylidenebenzosuberone derivatives with calf thymus DNA by TLC and UV–Vis methods, a DNA cleavage study

Interaction of some cyclic chalcone analogs, (E)-2-(4′-X-benzylidene)-1-benzosuberone derivatives, with calf thymus DNA has been investigated using thin-layer chromatographic and UV–Vis spectroscopic methods. Interaction of the compounds with calf thymus DNA exhibited relatively high intrinsic binding constants in the range of 3.1 × 104–1.0 × 105 M−1. The results indicate existence of weak, non-covalent interactions between the investigated chalcones with calf thymus DNA. Furthermore, the DNA cleavage activity of the compounds was studied by means of agarose gel electrophoresis. Each compound showed a slight DNA cleavage activity with pBR322. The obtained results provide additional knowledge on the previously documented cytotoxicity against several tumor cell lines of the cyclic chalcone analogs.

(E)-2-benzylidenebenzocyclanones: Part X. Determination of log P of (E)-3-benzylidene-2,3-dihydro-1-benzopyran-4-ones by RP-TLC. Effect on log P of incorporation of oxygen atom into carbocyclic chalcone analogues

log P values of 14 biologically active (E)-3-(X-benzylidene)-2,3-dihydro-1-benzopyran-4-ones (3) have been determined by an optimized and validated reversed-phase thin-layer chromatography (RPTLC) method. The RP-TLC investigations were performed on silanized silica gel 60F254 as stationary phase with methanol-water 60:40 (v/v) as mobile phase. The RP-TLC method was validated by analysis of four drugs, diazepam, progesterone, PGE1 ethyl ester, and itraconazole, with known log PSF (shake-flask) values. The experimentally determined log PTLC values were compared with the predicted log P values obtained by the CLOGP program. The log PTLC values of the investigated (E)-3-(X-benzylidene)-2,3-dihydro-1-benzopyran-4-ones (3) were compared with those of the previously investigated structurally related chalcones (1) and (E)-2-(X-benzylidene)-1-tetralones (2). It was found that the log PTLC values of the respective 4′-X-benzylidene analogues increased in the 1 < 3 < 2 order. The average difference between the log PTLC data of the respective cyclic 4′-X-benzylidene derivatives 2 and 3 was found to be 0.23 log P unit. The effect of the position (ortho, meta, or para) of the aromatic substituents did not follow regularity in either of the two series. The results indicate the importance of both steric and electronic factors in the lipophilicity of the investigated compounds.