Piperazine skeleton in the structural modification of natural products: a review

Abstract

Piperazine moiety is a cyclic molecule containing two nitrogen atoms in positions 1 and 4, as well as four carbon atoms. Piperazine is one of the most sought heterocyclics for the development of new drug candidates with a wide range of applications. Over 100 molecules with a broad range of bioactivities, including antitumor, antibacterial, anti-inflammatory, antioxidant, and other activities, were reviewed. This article reviewed investigations regarding piperazine groups for the modification of natural product derivatives in the last decade, highlighting parameters that affect their biological activity.

Keywords: Piperazine; natural product; pharmacological activity; structure–activity relationship.

Figure 1.

Chemical structures of flavone and its derivative.

Figure 2.

Chemical structures of chrysin and its derivative.

Figure 3.

Chemical structures of oroxylin A and its derivatives.

Figure 4.

Chemical structures of chalcone and its derivatives.

Figure 5.

Chemical structures of resveratrol and its derivatives.

Figure 6.

Chemical structures of gambogic acid and its derivative.

Figure 7.

Chemical structures of wogonin and its derivative.

Figure 8.

Chemical structures of quercetin and its derivative.

Figure 9.

Chemical structures of chenodeoxycholic acid and its derivative.

Figure 10.

Chemical structures of ursolic acid and its derivative.

Figure 11.

Chemical structures of oleanolic acid and its derivative.

Figure 12.

Chemical structures of asiatic acid and its derivatives.

Figure 13.

Chemical structures of hederagenin and its derivatives.

Figure 14.

The structure of pentacyclic triterpenoid AKBA.

Figure 15.

Chemical structures of dehydroabietic acid and its derivatives.

Figure 16.

Chemical structures of celastrol and its derivatives.

Figure 17.

Chemical structures of artemisinin and its derivatives.

Figure 18.

Chemical structures of emodin and its derivatives.

Figure 19.

Chemical structures of bergenin and its derivatives.

Figure 20.

Chemical structures of glycyrrhetic acid and its derivatives.

Figure 21.

Chemical structures of combretastatin-A4 and its derivatives.

Figure 22.

Chemical structures of colchicine and its derivatives.

Figure 23.

Chemical structures of sarsasapogenin and its derivatives.

Figure 24.

Chemical structures of berberine and its derivatives.

Figure 25.

Chemical structures of oestrone and its derivatives.

Figure 26.

Chemical structures of matrine and its derivatives.

Figure 27.

Chemical structures of purine and its derivatives.

Figure 28.

Chemical structures of steroid derivatives.

Figure 29.

Chemical structures of camptothecin and its derivatives.

Figure 30.

Chemical structures of benzo-α-pyrone and its derivatives.

Figure 31.

Chemical structures of myricetin and its derivatives.

Figure 32.

Chemical structures of podophyllotoxin and its derivatives.

Figure 33.

Chemical structures of lanosterol and its derivatives.

Figure 34.

Chemical structures of anthraquinone and its derivatives.

Figure 35.

Chemical structures of piperazinylquinolone skeleton.

Figure 36.

Chemical structures of glycyrrhetinic acid and its derivatives.

Figure 37.

Chemical structures of 5,8-dihydropteridine-6,7-dione and its derivatives.

Figure 38.

Chemical structures of vindoline and its derivative.

Figure 39.

Chemical structures of indirubin and its derivative.

Figure 40.

Chemical structures of baicalein and its derivative.

Figure 41.

Chemical structures of apigenin and its derivative.

Figure 42.

Chemical structures of pulsatilla saponin A and its derivatives.

Figure 43.

Chemical structures of betulonic acid and its derivatives.

Figure 44.

Chemical structures of coumarin and its derivatives.

Figure 45.

Chemical structures of flavone derivatives.

Figure 46.

Chemical structures of pleuromutilin and its derivatives.

Figure 47.

Chemical structures of chrysin and its derivatives.

Figure 48.

Chemical structures of 1,5-diphenyl-2-penten-1-one and its analogs.

Figure 49.

Chemical structures of curcumin.

Figure 50.

Chemical structures of glycyrrhetinic acid and its derivatives.

Figure 51.

Chemical structures of ursolic acid and its derivatives.

Figure 52.

Chemical structures of chromen derivatives.

Figure 53.

Chemical structures of flavone derivatives.

Figure 54.

Chemical structures of chalcones derivative.

Figure 55.

Chemical structures of chalcone-biscoumarin derivative.

Figure 56.

Chemical structures of glycyrrhetic acid and its derivative.

Figure 57.

Chemical structures of smilagenin and its derivatives.

Figure 58.

Chemical structures of coumarin and its derivatives.

Figure 59.

Chemical structures of berberine and its derivatives.

Figure 60.

Chemical structures of piperazinyl flavone derivatives.

Figure 61.

Chemical structures of curcumin and its derivative.

Figure 62.

Chemical structures of tacrine and its derivative.

Figure 63.

Chemical structures of sarsasapogenin and its derivatives.

Figure 64.

Chemical structures of genipin and its analog.

Figure 65.

Chemical structures of coumarin and its derivatives.

Figure 66.

Chemical structures of coumarin and its derivatives.

Figure 67.

Chemical structures of tropolone and its derivative.

Figure 68.

Chemical structures of baicalein and its derivative.

Figure 69.

Chemical structures of xanthone and its derivatives.

Figure 70.

Chemical structures of xanthone and its derivatives.

Figure 71.

Chemical structures of 7,8-dihydroxy-3-methyl-isochromanone-4 (XJP) and its derivatives.

Figure 72.

Chemical structures of artemisinin and its derivatives.

Figure 73.

Chemical structures of echinocystic acid and its derivatives.

Figure 74.

Chemical structures of berberrubine and its derivative.

Figure 75.

Chemical structures of kojic acid and its derivative.

Figure 76.

Chemical structures of oleanolic acid and its derivatives.

Figure 77.

Chemical structures of adenosine and its analog.