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. This 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.

Naturally occurring chalcones and their biological activities

Aldose reductase, the key enzyme of the polyol pathway, and oxidative stress are known to play important roles in the complications of diabetes. A drug with potent inhibition of aldose reductase and oxidative stress, therefore, would be a most promising drug for the prevention of diabetic complications. The purpose of this study was to develop new compounds with these dual-effects through synthesis of chalcone derivatives and by examining the structure-activity relationships on the inhibition of rat lens aldose reductase as well as on antioxidant effects. A series of 35 flavonoid derivatives were synthesized by Winget's condensation, oxidation, and reduction of appropriate acetophenones with appropriate benzaldehydes. The inhibitory activity of these derivatives on rat lens aldose reductase and their antioxidant effects, measured using Cu2+ chelation and radical scavenging activities on 1,1-diphenyl-picrylhydrazyl in-vitro, were evaluated. Their effect on sorbitol accumulation in the red blood cells, lenses and sciatic nerves of streptozotocin-induced diabetic rats was also estimated. Among the new flavonoid derivatives synthesized, those with the 2′,4′-dihydroxyl groups in the A ring such as 2,4,2′,4′-tetrahydroxychalcone (22), 2,2′,4′-trihydroxychalcone (11), 2′,4′-dihydroxy-2,4-dimethylchalcone (21) and 3,4,2′,4′-tetrahydroxychalcone (18) were found to possess the highest rat lens aldose reductase inhibitory activity in-vitro, their IC50 values (concentration of inhibitors giving 50% inhibition of enzyme activity) being 1.6 times 10−7, 3.8 times 10−7, 4.0 times 10−7 and 4.6 times 10−7 M, respectively. All of the chalcones tested except 3, 18, 23 with o-dihydroxy or hydroquinone moiety showed a weak free radical scavenging activity. In the in-vivo experiments, however, compound 18 with o-dihydroxy moiety in the B ring showed the strongest inhibitory activity in the accumulation of sorbitol in the tissues. It also showed the strongest activity in transition metal chelation and free radical scavenging activity. Of the 35 4,2′-dihydroxyl and 2′,4′-dihydroxyl derivatives of flavonoid synthesized, including chalcone, flavone, flavanone, flavonol and dihydrochalcone, some chalcone derivatives synthesized were found to possess aldose reductase inhibition and antioxidant activities in-vitro as well as inhibition in the accumulation of sorbitol in the tissues in-vivo. 3,4,2′,4′-Tetrahydroxychalcone (18, butein) was the most promising compound for the prevention or treatment of diabetic complications.

Synthesis of flavonoids and their effects on aldose reductase and sorbitol accumulation in streptozotocin-induced diabetic rat tissues.

Contents1. Introduction2. Chemical Constituents2.1. Monoterpenes2.1.1. Nepetalactones and Related Compounds2.1.2. Iridoid Glucosides2.1.3. Other Monoterpenes2.2. Sesquiterpenes2.3. Diterpenes2.4. Triterpenes2.5. Flavonoids2.6. Phenols2.7. Essential Oils2.8. Others3. Biological Activities3.1. Activity on Central Nervous System3.2. Antibacterial, Antifungal, and Antiviral Activities3.3. Antioxidant Activity3.4. Antinociceptive, Analgesic, and Anti-Inflammatory Activities3.5. Cytotoxic Activity3.6. Phytotoxic Activity3.7. Spasmolytic and Bronchodilatory Activities3.8. Anti-Atherosclerotic Activity3.9. Vasorelaxant and Platelet-Aggregation Activity3.10. Feline-Attractant and Insect-Repellent Activities4. Concluding Remarks1. Introduction. – The genus Nepeta, one of the largest genera of the Lamiaceaefamily, belongs to the subfamily Nepetoideae and tribe Mentheae. It comprises ca. 300herbaceous perennial, rarely annual species most of which are spread out over thelarger part of central and southern Europe, the Near East, central and southern Asia,and some areas of Africa. The plants of this genus have beautiful flowers with apleasantodor;thepollengrainsarehexacolpate[1].Thegreatestdiversityandrichness

Chemical constituents and biological activities of Nepeta species.

Capillary electrophoresis of phytochemical substances

Comparative phytochemical and morphological analyses of three Italian Primula species

A new dihydroxy chalcone has been isolated from the EtOAc-soluble portion of the whole plant of Primula macrophylla, and its structure was determined by spectroscopic methods, including 2D nmr, as 3,3'-dihydroxychalcone [1]. 3'-Methoxyflavone and β-sitosterol have also been isolated for the first time from this plant

Isolation of 3,3'-dihydroxychalcone from Primula macrophylla

A new triterpenoidal aldehyde, nepehinal ( 1), has been isolated from the alcoholic extract of the whole plant of NEPETA HINDOSTANA. Its structure was established as 1beta,3beta,1 1alpha-trihydroxy-lup-20(29)-en-30-al through chemical and spectroscopic studies including two dimensional NMR. (13)C-NMR spectral assignments of nepeticin ( 2) have also been revised.

Nepehinal: A New Triterpenoidal Aldehyde from Nepeta hindostana.

Macrophylloside, a flavone glucoside from Primula macrophylla

Macrophyllicin, a saponin from Primula macrophylla.

A new triterpenoid saponin, designated macrophyllicinin [1], has been isolated from the MeOH extract of the whole plant of Primula macrophylla. Its structure was established by chemical and spectroscopic means as 3 beta-O-[alpha-L-rhamnopyranosyl-(-->2)-beta-D-glucopyranosyl-(-->2)- beta-D-galactopyranosyl-(-->2)-beta-D-glucuronopyranosyl]-6 beta,16 alpha-dihydroxyolean-12-en-28-acetate. The aglycone 2 of this saponin is also a new compound.

Mohammad Ghani Shah

Papers

Isolation of 3,3'-dihydroxychalcone from Primula macrophylla

Nepehinal: A New Triterpenoidal Aldehyde from Nepeta hindostana.

Macrophylloside, a flavone glucoside from Primula macrophylla

Macrophyllicin, a saponin from Primula macrophylla.

Macrophyllicinin, a saponin from Primula macrophylla.