inflammation is a physiological reactionwhich involves cellular and biochemical responses , which is not only symptom for common diseases but also known to be an early phase for some serious diseases such as alzheimer 's disease , cancer , heart vascular diseases   etc . nonsteroidal anti - inflammatory drugs ( nsaids ) like ketoprofen , ibuprofen , aceclofenac , and so forth under current clinical usage for the treatment of inflammation , algesia and pyresis   are associated with major drawbacks of gastrointestinal disorders like dyspepsia , gastric ulcers , and so forth , due to the direct contact of free carboxylic group with the gastric mucosa [ 3 , 4 ] and due to decrease in production of prostaglandins in tissue . in order to overcome these drawbacks , there is an urgent need for design and synthesis of new chemical entities with excellent anti - inflammatory response and minimum side effects . hydrazones constitute a versatile compound of organic class having the basic structure r1r2c = nnr3r4 [ 7 , 8 ] . two nitrogen atoms of hydrazone are nucleophilic but the amino type nitrogen is more reactive , whereas the carbon atom possesses both characters , that is , nucleophilic and electrophilic . the active centers of hydrazine , that is , carbon and nitrogen , are mainly responsible for the physical and chemical properties of the hydrazones and , due to the reactivity toward electrophiles and nucleophiles , hydrazones are used for the synthesis of organic compound such as heterocyclic compounds [ 9 , 10 ] . the general method for the synthesis of the hydrazones is the reaction of hydrazine with carbonyl compounds such as aldehydes or ketones in solvents like ethanol , methanol , butanol [ 1113 ] , and so forth . hydrazones and their derivatives are known to exhibit interesting diverse biological activities like antioxidant , anti - inflammatory [ 15 , 16 ] , anticonvulsant [ 17 , 18 ] , analgesic [ 19 , 20 ] , antimicrobial [ 2123 ] , anticancer [ 24 , 25 ] , antiprotozoal , antiparasitic , cardioprotective , antidepressant , antitubercular [ 30 , 31 ] , anti - hiv , and trypanocidaletc . hydrazones are also used to couple with certain drugs and the bonds based on hydrazones are stable at the neutral ph . the hydrazone schiff bases of aroyl , acyl , and heteroaroyl compounds are known to have an additional donor site , that is , c = o , which make them more versatile and flexible . this versatility has leaded the hydrazones to emerge as good chelating agents that can form a variety of complexes with different transition metals . some hydrazones have been introduced by the researchers as potent drugs , such as nifuroxazide , an intestinal antiseptic [ 34 , 35 ] , dihydralazine as hypertensive , and gyromitrin , a toxin . a series of benzothiazine n - acylhydrazones 1(a  h ) was designed by structural modification of piroxicam and synthesized and evaluated for the anti - inflammatory and antinociceptive activities ( figure 1 ) . the pharmacological screening revealed that compounds 1(a  h ) have exhibited better activity than standard drug piroxicam . compounds 1f and 1 g were identified as new anti - inflammatory and antinociceptive agents which were capable of inhibiting cell recruitment by 70% and 80% , respectively , at dose of 100  mol / kg , p.o in zymosan- and carrageenan - induced peritonitis . a novel series of 6-substituted-3(2h)-pyridazinone-2-acetyl-2(p - substituted / nonsubstituted benzal)hydrazine 2(a i ) was synthesized and evaluated for their analgesic and anti - inflammatory activity ( figure 2 ) . the activity was evaluated by using carrageenan - induced paw oedema assay and indomethacin was employed as standard for comparison of results . the results revealed that 6-substituted-3(2h)-pyridazinone-2-acetyl-2(nonsubstitutedbenzal)hydrazones , that is , 2a , 2b , and 2c , were found to be most potent anti - inflammatory agents . compound 2a , 6-[4-(3-chlorophenyl)piperazine]-3(2h)-pyridazinone-2-acetyl-2(p - substituted / nonsubstituted benzal)hydrazine , was found to be slightly better than standard drug indomethacin . a novel series of n-(substituted benzylidene)-2-(n-(4h-1,2,4-triazole-4-yl ) benzamido)acetohydrazide derivatives 3(a  j ) was synthesized and evaluated for the anti - inflammatory and antimicrobial activity ( figure 3 ) . indomethacin was used as standard drug and carrageenan - induced paw oedema method was employed for the anti - inflammatory screening of the test compounds . it was found that compounds 3f , 3 g , and 3j substituted with 4-chloro , 4-dimethylamino , and 4-nitro exhibited 66.7 , 61.7 , and 63.2% inhibition , respectively , at 50  mg / kg , oral dose , whereas standard drug indomethacin had shown 64.2% inhibition at 10  mg / kg , oral dose . synthesis of a novel series of some amidine and hydrazone derivatives 4 was reported ( figure 4 ) . the synthesized compounds were further subjected to evaluation of anti - inflammatory and analgesic activities . anti - inflammatory activity evaluation was carried out using carrageenan - induced rat paw oedema assay and compound 4a was found to have good anti - inflammatory activity . a series of nineteen pyrazine n - acylhydrazone ( nah ) derivatives 5(a  s ) was ( figure 5 ) designed by molecular simplification of the prototype ( lassbio-1018 ) , a nonselective cyclooxygenase inhibitor . synthesis of the designed compounds was carried out and they were evaluated for their anti - inflammatory and analgesic activities in several animal models of pain and inflammation like writhing test , formalin test , hot plate test , zymosan - induced peritonitis , capsaicin - induced ear edema , and freund 's adjuvant - induced arthritis model . thalidomide ( tnf- inhibitor ) , celecoxib ( cox-2 ) inhibitor , and indomethacin ( selective cox-1 inhibitor ) were employed as standard drugs . results enlightened that compound 5o ( 2-n-[(e)-(3,4,5-trimethoxyphenyl)methylidene]-2-pyrazinecarbohydrazide , lassbio-1181 , had better pharmacological activities and can be used as a lead compound for development of new analgesic and anti - inflammatory agents . a novel series of isatin derivatives , that is , isatin-3-[n2-(2-benzalaminothiazol-4-yl)]hydrazones 6(a  j ) , was synthesized and evaluated for anti - inflammatory , analgesic , and antipyretic activities ( figure 6 ) . carrageenan - induced rat paw oedema model was used for evaluation of anti - inflammatory activity and indomethacin was employed as standard drug . it was found that the compounds 6f , 6h , and 6j substituted at fifith position with methyl , chloro , and nitro groups , respectively , exhibited significant anti - inflammatory activity . synthesis of a novel series of orally active n - phenylpyrazolyl - n - glycinyl - hydrazone derivatives , 7a  g ( figure 7 ) and 8 ( figure 8) , was carried out . synthesized compounds were evaluated for their in vivo analgesic and anti - inflammatory activities and in vitro inhibition of tnf- ( tumor necrosis factor ) . compounds 7a , ( e)-2-(3-tert - butyl-1-phenyl-1h - pyrazol-5-ylamino)-n-((4-(2-morpholinoethoxy)naphthalen-1-yl ) methylene)acetohydrazide , and 7f , ( e)-2-(3-tert - butyl-1-phenyl-1h - pyrazol-5-ylamino)-n-(4-chlorobenzylidene)acetohydrazide , were known to possess anti - inflammatory activities when compared to the standard drug used , that is , sb-203580 . n ) ( figure 9 ) was reported and evaluated for their in vitro anti - inflammatory , antimicrobial and antioxidant activities . albumin denaturation studies were carried out in order to evaluate the anti - inflammatory activity by employing diclofenac sodium as standard . compounds 9c , 9d , and 9e were reported to have good anti - inflammatory activity due to presence of 4-nitro , 4-methyl , and 2-hydroxy groups , respectively , whereas 9e was found to be the most active anti - inflammatory agent . synthesis and biological evaluation of some new benz[b]thiophene derivatives like thiadiazole , pyrazoline , oxadiazole and diaryl pyrazoles was carried out . n-(3- chlorobenzo[b]thiophene-2-carbonyl)-3-methyl-4 - 9 substituted phenylhydrazono pyrazolin-5-one 10(a - e ) were subjected to anti - inflammatory and antimicrobial evaluation ( figure 10 ) . compound 10b substituted with 2-nitro-4-methyl was found to have 50.25 % inhibition which is near about the standard drug diclofenac sodium i.e. 51.88% . synthesis of zinc complexes 11 , [ zn(lassbio-466)h2o]2 of salicylaldehyde 2-chlorobenzoyl hydrazone ( h2lassbio-466 ) , and 12 , [ zn(hlassbio-1064)cl]2 salicylaldehyde 4-chlorobenzoyl hydrazone ( h2lassbio-1064 ) , was carried out . the complexes were further subjected to evaluation for peripheral and central nociception and acute inflammation in animal models . both of the complexes exhibited anti - inflammatory activity . complex 11 has shown activity in both phases of formalin test like indomethacin and indicated its ability to inhibit nociception associated with the inflammatory response , whereas h2lassbio-466 was active only in first phase of formalin test . synthesis of some new hydrazide derivatives of 2-napthoxy acetic acid , nicotinic acid [ 47 , 48 ] and napthlene-1-acetic acid   has been reported . out of these hydrazide derivatives most active antimicrobial compounds carrageenan induced rat paw oedema model was employed for the evaluation of theses active compounds using diclofenac sodium as standard drug . results revealed that naphthalen-1-yloxy)-acetic acid [ 1-(2-bromo-4-cyano - phenyl)-ethylidene]-hydrazide 13 ( figure 11 ) has shown percent inhibition of 20.90% at a dose of 50  mg / kg . the nicotinic acid hydrazide derivatives , 14a and 14b , substituted with nitro group at meta and ortho positions , respectively , were found to be the most active anti - inflammatory agents ( figure 12 ) . the percent inhibition of compounds 14a and 14b was found to be 37.29% and 35.73% , respectively , at the dose of 20  mg / kg and 34.17% and 25.12% , respectively , at the dose of 50  mg / kg , whereas percent inhibition of diclofenac sodium was found to be 38.85% . the conclusion drawn from the results was that the substitution of nitro group and halogens contributed to anti - inflammatory activity . synthesis of benzophenone semicarbazone ( bsc ) 15a and acetophenone semicarbazone ( asc ) 15b was carried out ( figure 13 ) . the anti - inflammatory activity was determined on swiss albino mice by using carrageenan - induced mice paw oedema model . both of the compounds were screened at two different doses , that is , 25  mg / kg and 50  mg / kg ( p.o . ) . compound 15a showed 36.6% and 46.6% of inhibition at 25  mg / kg and 50  mg / kg , respectively , whereas compound 15b showed 34.6% and 41.5% inhibition . diclofenac sodium was used as standard drug which showed 70.29% inhibition at 10  mg / kg ( p.o . ) . from the above observations , it was concluded that both of the test compounds possessed anti - inflammatory activity . a novel series of 2-[4-(substituted benzylideneamino)-5-(substituted phenoxymethyl)-4h-1,2,4-triazol-3-yl thio]acetic acid , 16(a all the newly synthesized compounds were evaluated for in vivo anti - inflammatory and analgesic activities . among the series 16d , 16e , 16j , and 16k showed significant activity with 63.4% , 62.0% , 64.1% , and 62.5% edema inhibition , respectively , as compared to standard drug diclofenac 67.0% after the third hour . compounds 16 g , 16h , 16i , and 16l showed good anti - inflammatory activity , whereas compounds 16a  c and 16f were found to be the least active . the results enlightened the effect of electron withdrawing moiety , that is , chloro group on the anti - inflammatory activity . a series of bis - hydrazone derivatives , that is , ( z)-n,n-(1-(4-substituted phenyl)ethene-1,2-diyl)bis(4-substituted benzhydrazide ) , 17(a d ) , was synthesized by reaction of 2-chloro-1-(4-chloro phenyl)ethanone or 2-bromo-1-(4-bromophenyl)ethanone with acid hydrazides ( figure 15 ) . all the synthesized compounds were evaluated for the anti - inflammatory , analgesic , and ulcerogenic activities . formalin - induced rat paw oedema model was selected and ketoprofen was employed as standard drug . all compounds were found to exhibit good anti - inflammatory activity with percent inhibition of 68.4% and 61.4% of compounds synthesis of a series of hydrazone derivatives , that is , n-(substituted benzylidene)-3-cyclohexylpropionic acid hydrazide , 18(a inducible nitric oxide synthase ( inos ) and nf-b were selected for determination of anti - inflammatory activity . compounds 18c , 18e , and 18i were more active than the other synthesized compounds which proved that there is a positive correlation between the inhibitions of inos activity and functional groups , that is , methyl , fluoro , and isopropyl , on phenyl ring . inhibition of nf- b mediated transcription was seen in human chondrosarcoma ( sw1353 ) cells and compounds 18a , 18c , and 18h have shown inhibition with ic50 values of 6.9 , 7.7 , and 6.4  g / ml , respectively ( figure 17 ) . this observation correlated that methyl and chloro groups have a considerable influence on the inhibition of nf-b mediated transcription . the other compounds 18d , 18e , 18 g , and 18i inhibited the nf-b activity to a lesser extent with ic50 values in the range of 1014  g / ml . compounds 18b , 18d , and 18j were found to be comparatively less active than other compounds . from the results , it was concluded that substitutions at para position of phenyl ring had significant influence on anti - inflammatory activity . by application of molecular hybridization approach design , and synthesis of thirty two furoxanyl n - acylhydrazones(furoxanyl - nah ) synthesized compounds were evaluated for their in vitro as well as in - vivo analgesic and anti - inflammatory activities . the in vitro anti - inflammatory activity was evaluated by decrease in nf-b activation and interleukin-8 inhibition by using a human pathway - specific reporter cell system ( ht-29-nf-b - hrgfp ) whereas carrageenan induced paw oedema was used for in vivo evaluation of anti - inflammatory activity . furoxanyl - nah 19 ( figure 17)and benzofuroxanyl - derivative 20 ( figure 18 ) were reported to have orally anti - inflammatory and analgesic activities without interleukin-8 inhibition . furoxanyl - nah derivative 21a ( figure 19)was emerged as a structural lead to develop new lipoxygenase ( lox ) inhibitors . the active derivatives 19 , 21a and 21b were found to be less mutagenic and were proposed as candidates for the further clinical studies . synthesis of a series of novel acyl - hydrazones bearing 2-aryl - thiazole moiety was carried out . the synthesized compounds were screened for invivo anti - inflammatory activity by evaluating three parameters , that is , nitric oxide synthesis , phagocytes activity , and acute phase bone marrow response , in acute experimental inflammation . compounds 22c , 22e , 22f , 24b , and 26b were found to have a good inhibitory effect on the acute phase marrow response by reducing the absolute leukocytes count due to the lower neutrophils percentage . compound 22c ( figure 20 ) with 2-phenyl - thiazole and [ 2-(4-methylphenyl)-4-methylen]-thiazole hydrazine moieties was proved to be a more potent inhibitor of the acute phase bone marrow response than meloxicam , the anti - inflammatory standard drug . phagocytic activity was assessed by calculating phagocytic index ( pi ) and the phagocytic activity ( pa ) . all the newly synthesized compounds reduced pi significantly and compounds 22a ( figure 20 ) , 22b ( figure 20 ) , 22d ( figure 20 ) , 23b ( figure 21 ) , 24b ( figure 22 ) , 25 ( figure 23 ) and 26b ( figure 24)were observed as more potent inhibitors than meloxicam . pa was significantly reduced by the compounds 22a , 22d , 23b , 24b , 23c , 25 and 26b from which 22a , 22d , 20 and 26b were found to be more potent inhibitors than meloxicam . the no synthesis was significantly reduced by 22a , 22b , 23c , 26a , and 26b and they all , except for 26a , displayed a stronger inhibitory activity than meloxicam . synthesis of a novel series of phthalic anhydride based substituted benzylidene - hydrazide derivatives , 27a all the synthesized derivatives were screened for in vivo anti - inflammatory and analgesic activities by carrageenan - induced rat paw oedema and tail immersion methods , respectively , using diclofenac sodium as standard drug . the results revealed that derivatives 27d , 27e , and 27h ( figure 25 ) have shown potent anti - inflammatory activity with percentage inhibition of 58.6% , 61.4% , and 64.0% , respectively , which is comparable with standard drug diclofenac sodium , that is , 68.0% . the reaction time of derivatives 27d and 27h that was found to be 8.91  0.21 and 9.09  0.03 , respectively , after 90 minutes which is comparable with reaction time of diclofenac sodium ( 10.93  0.01 ) after 90 minutes has shown analgesic potency of these derivatives . hydrazone derivatives are well known to have various important pharmacological activities and are used for synthesis of a wide variety of medicinally active compounds . this review paper summarizes the anti - inflammatory potential of hydrazone derivatives and the effect of substitutions of different groups on the anti - inflammatory activity . this summarized study is an attempt to bring about the anti - inflammatory activity for awaking the safe use of this important chemical moiety with minimal or no ulcerogenic effects in future .
hydrazones are a special class of organic compounds in the schiff base family . 
 hydrazones constitute a versatile compound of organic class having basic structure ( r1r2c = nnr3r4 ) . 
 the active centers of hydrazone , that is , carbon and nitrogen , are mainly responsible for the physical and chemical properties of the hydrazones and , due to the reactivity toward electrophiles and nucleophiles , hydrazones are used for the synthesis of organic compound such as heterocyclic compounds with a variety of biological activities . 
 hydrazones and their derivatives are known to exhibit a wide range of interesting biological activities like antioxidant , anti - inflammatory , anticonvulsant , analgesic , antimicrobial , anticancer , antiprotozoal , antioxidant , antiparasitic , antiplatelet , cardioprotective , anthelmintic , antidiabetic , antitubercular , trypanocidal , anti - hiv , and so forth . 
 the present review summarizes the efficiency of hydrazones as potent anti - inflammatory agents .