Pharmaceutical Chemistry Studies on the Anthelmintic Property of Aminobenzylated Mannich Bases ChaluvaraMu KC Bhat KI 'HSDUWPHQWRI3KDUPDFHXWLFDO&KHPLVWU\*RYHUQPHQW&ROOHJHRI3KDUPDF\%DQJDORUH,QGLD Address for correspondence:'U.&&KDOXYDUDMX(PDLOFKDOXYDUDMXNF#JPDLOFRP ABSTRACT Studies were conducted on the anthelmintic property of about 15(e-h, 1e-1h, 2d-2f and 3e-3h) synthesized DPLQREHQ]\ODWHG0DQQLFKEDVHVEHDULQJ1PHWK\OSLSHUD]LQHXVLQJ,QGLDQHDUWKZRUPVPheritima posthuma DJDLQVWSLSHUD]LQHFLWUDWHDVVWDQGDUGUHIHUHQFH7KUHHFRQFHQWUDWLRQVRIHDFKFRPSRXQG ZY were studied, which involved the determination of paralysis and death time of the worms. The compound 1g H[KLELWHGWKHPRVWVLJQL¿FDQWDQWKHOPLQWLFDFWLYLW\DPRQJDOOWKHFRPSRXQGVVFUHHQHGDJDLQVWWKHZRUPVDV compared to standard drug. Key words: $PLGHVDPLQREHQ]\ODWHG0DQQLFKEDVHVDQWKHOPLQWLFSURSHUW\Pheritima posthuma, piperazine citrate INTRODUCTION DSRWRVLVHWFDQGWKHEHQ]LPLGD]ROHLPLGD]RWKLD]ROH DQGPDFURF\FOLFODFWRQHV·FODVVRI GUXJVKDYHEHFRPHD Diseases caused by helminth parasites in livestock global phenomenon in gastrointestinal nematodes of farm continue to be a major productivity constraint, especially animals, hence there is a need for an anthelmintic with VPDOOUKPLQDQWVLQWKHWURSLFVDQGVXEWURSLFV,QIHFWLRQV OHVVHUVLGHHIIHFWV$OVRGXHWRHVFDODWLQJFRVWVRI UHVHDUFK by gastrointestinal helminth parasites of livestock are and development and limited commercial attractiveness, among the most common and economically important investment in research for new drug development for GLVHDVHVRI JUD]LQJOLYHVWRFN[1]9DULRXVGUXJVXVHGIRUWKH tropical diseases is much less as compared to other cure of helminth infections are triimidazoles, bithional, GLVHDVHV parabendazole, mebendazole, oxfendazole, niclosamide DQGSLSHUD]LQHHWF+RZHYHUGUXJVOLNHPHEHQGD]ROH ,WLVZHOOGRFXPHQWHGLQWKHOLWHUDWXUHWKDW0DQQLFKEDVHV have considerable side-effects such as mitotic arrest and are known to possess pharmacologically proven therapeutic potentials[2]DQGWKH\ÀQGDSSOLFDWLRQDVDQWLPLFURELDO[3] Access this article online antitubercular,[4] antimalarial,[5] anticancer[6] and local 4uicN Response Code: DQHVWKHWLFGUXJV[7] Though extensive research work has Website: www.jyoungpharm.in EHHQUHSRUWHGRQ0DQQLFKEDVHVUHODWLYHO\YHU\OLWWOHLV NQRZQVRIDUDERXWDPLQREHQ]\ODWHG0DQQLFKEDVHV[8,9] of DOI: 1PHWK\OSLSHUD]LQHDQGWKHOLWHUDWXUHUHYLHZUHYHDOHGWKDW 10.4103/0975-1483.83775 piperazine and related compounds are known to possess DQWKHOPLQWLFDFWLYLW\[10] This enthused us to evaluate some Journal of Young Pharmacists Vol 3 / No 3 243 Chaluvaraju and Bhat: Anthelmintic activity of aminobenzylated Manich bases of the synthesized[11-14] DPLQREHQ]\ODWHG0DQQLFKEDVHV UHDGLQJZDVWDNHQLQWULSOLFDWH 7KHWLPHWDNHQE\ZRUPV >)LJXUH@IRUDQWKHOPLQWLFSURSHUW\LQWKHSUHVHQWVWXG\ to become motionless was noted as paralysis time and to $QWKHOPLQWLFDFWLYLW\RI WKHV\QWKHVL]HGFRPSRXQGV 7DEOH$QWKHOPLQWLFDFWLYLW\RIFRPSRXQGV HKH KGIHK The study of anthelmintic activity was carried out according Test compound &RQFHQWUDWLRQ Time in minutes WRWKHPHWKRGRI $MDLJHRED[15]XVLQJ,QGLDQHDUWKZRUP )RUSDUDO\VLV For death Pheritima posthuma due to its anatomical and physiological Control (Normal saline) 0.9 – – resemblance with the intestinal round worm parasites of Piperazine citrate(Std) 0.1 52 80 [16,17] 0.2 43 75 KXPDQEHLQJV Pheritima posthuma of nearly equal size 0.3 35 66 FP ZHUHFROOHFWHGIURPZDWHUORJJHGDUHDVRI IRUW e 0.1 94 130 ODNHLQ0DQG\DGLVWULFW.DUQDWDND,QGLDIRUWKHSUHVHQW R = -NHCONH- 0.2 82 121 VWXG\ R2 = P-N (CH3)2 0.3 70 109 f 0.1 99 129 R = -NHCSNH- 0.2 91 120 MATERIA/S AND MET+ODS R2 = P-N (CH3)2 0.3 83 107 g 0.1 91 131 3UHSDUDWLRQRI VDPSOHVROXWLRQV R =-NHCOCH3 0.2 83 118 R2 = P-N (CH3)2 0.3 78 105 The suspensions of the sample[18] ZYZYDQG h 0.1 102 142 R =-NHCOC H 0.2 96 131 ZY ZHUHSUHSDUHGE\WULWXUDWLQJWKHFRPSRXQGVZLWK 6 5 R = P-N (CH ) 0.3 84 119 GLVWLOOHGZDWHUDQGZYWZHHQDQGIXUWKHUWUDQVIHUUHG 2 3 2 WRDEHDNHUODEHOHGDVDQGUHVSHFWLYHO\VWLUUHG 1e 0.1 86 135 R = NHCONH- 0.2 79 129 IRUDERXWPLQDWURRPWHPSHUDWXUH7KHUHVXOWLQJVROXWLRQV R2 = H 0.3 68 105 ZHUHWKHQXVHGIRUDQWKHOPLQWLFVWXGLHV 1f 0.1 79 125 S 0.2 70 113 Method of testing HH|| R = ----NCN )LIW\ÀYHJURXSVRI DSSUR[LPDWHO\HTXDOVL]HG FP R = H 0.3 61 100 1g 0.1 68 110 ,QGLDQHDUWKZRUPVPheritima posthama consisting of six R = NHCOCH 0.2 53 99 earthworms in each group were placed in Petri dishes 3 R2 = H 0.3 49 87 µVL]H FRQWDLQLQJVXVSHQVLRQVRI VSHFLÀFFRQFHQWUDWLRQ 1h 0.1 72 121 ZY DWURRPWHPSHUDWXUH(DFKJURXS R = -NHCOC6H5 0.2 63 115 R = H 0.3 56 104 ZDVWUHDWHGZLWKRQHRI WKHIROORZLQJFRQWURO ZY 2 WZHHQLQQRUPDOVDOLQH SLSHUD]LQHFLWUDWH 2d 0.1 98 142 R = -NHCOC H N 0.2 91 129 ZYLQQRUPDOVDOLQH GLIIHUHQWFRQFHQWUDWLRQRI 4 3 2 R2 = H 0.3 84 120 FRPSRXQGV UHVSHFWLYHO\ 2e 0.1 115 161 R = -NH COC4H3N2 0.2 108 154 The times taken for complete paralysis and death were R2 =2,5-Dimethoxy 0.3 97 139 UHFRUGHGXVLQJDVWRSZDWFK7KHPHDQSDUDO\VLVWLPH 2f 0.1 111 150 R = - NH COC H N 0.2 102 141 and mean lethal time for each sample was recorded (each 4 3 2 R2 = 4- OH 0.3 93 130 3e 0.1 110 159 R = -NHCONH- 0.2 105 145 R2 = 3-NO2 0.3 97 132 3f 0.1 106 152 S 0.2 95 144 HH|| R = ----NCN R2 = 3-NO2 0.3 83 130 3g 0.1 119 169 R =-NHCOCH3 0.2 112 154 R2 = 3-NO2 0.3 101 138 3h 0.1 119 167 Figure 1: 5EJGOCVKETGRTGUGPVCVKQPQHEQORQWPFU GJGJFH R = -NH COC6H5 0.2 100 159 GJ R2 = 3-NO2 0.3 91 148 244 Journal of Young Pharmacists Vol 3 / No 3 Chaluvaraju and Bhat: Anthelmintic activity of aminobenzylated Manich bases note the death time the earthworms frequently applied with &KLSHOHPH$*XW-5RVHQWKDO-3&KLEDOH.6\QWKHVLVDQGELRORJLFDO HYDOXDWLRQRI SKHQROLF0DQQLFKEDVHVRI EHQ]DOGHK\GHDQG WKLR external stimuli by transferring them to a beaker containing semicarbazone derivatives against the cystiene protease falcipain-2 and a KRWZDWHULQRUGHUWRFKHFNLWVPRUWDOLW\7KHDQWKHOPLQWLF chloroquine resistant strain of Plasmodium falciparum%LRRUJ0HG&KHP activities of the tested compounds on Pheritima posthuma 6KLYDUDPD+ROOD%9HHUHQGUD%6KLYDQDQGD0.3RRMDU\%6\QWKHVLV HDUWKZRUP DUHLQGLFDWHGLQ7DEOH FKDUDFWHUL]DWLRQDQGDQWLFDQFHUDFWLYLW\VWXGLHVRQVRPH0DQQLFKEDVHV GHULYHGIURPWULD]ROHV(XU-0HG&KHP &KDWXUYHGL6&3DWQDLN*.'KDZDQ%1'L[LW9./RFDODQDHVWKHWLF RESU/TS AND DISCUSSION DFWLYLW\RI VRPHSDUDVXEVWLWXWHGDFHWRSKHQRQH0DQQLFKEDVHV,QGLDQ- 3KDUPDFRO The results of the anthelmintic activity exhibited by title 9DVR\D6/&KRYDWLD373XURKLW'+-RVKL6+*UHHQFKHPLVWU\DSSURDFK WRWKHV\QWKHVLVRI SRWHQWLDOO\ELRDFWLYHDPLQREHQ]\ODWHG0DQQLFKEDVHV compound on Pheritima posthumaDUHVKRZQLQ7DEOH WKURXJKDFWLYHK\GURJHQFRPSRXQGV-6HUE&KHP6RF $FORVHULQVSHFWLRQRI GDWDIURPWKLVWDEOHLQGLFDWHVWKDW 1LPDYDW.63RSXW6/9DVR\D6/-RVKL+66\QWKHVLVDQGDQWLPLFURELDO compound 1 g was found to possess markedly higher DFWLYLW\RI VRPHQHZDPLQREHQ]\ODWHG0DQQLFKEDVHV-,QGLDQ&KHP6RF anthelmintic activity than other compounds compared 7KH0HUFN,QGH[$Q(QF\FORSHGLDRI 'UXJV&KHPLFDOVDQG%LRORJLFDOV ZLWKVWDQGDUG%XWDOOWKHRWKHUFRPSRXQGVZHUHIRXQGWR 13thHG:KLWH+RXVH6WDWLRQ1HZ-HUVH\0HUFNDQG&R,QFS possess an interestingly low level of anthelmintic activity, &KDOXYDUDMX.&%KDW.,6\QWKHVLVDQGELRORJLFDODFWLYLW\RI VRPH ZKLFKLVDQRWHZRUWK\IHDWXUHRIWKHSUHVHQWVWXG\ DPLQREHQ]\ODWHG0DQQLFKEDVHVRI EHQ]DOGHK\GH&KHP$VLDQ- &KDOXYDUDMX.&%KDW.,6\QWKHVLVDQGIn-vitro study of novel amino- EHQ]\ODWHG0DQQLFKEDVHVDVDQWLEDFWHULDODJHQWV-,QGLDQ&RXQF&KHP ACKNOW/EDGMENT &KDOXYDUDMX.&%KDW.,6\QWKHVLVDQGDQWLPLFURELDODFWLYLW\RI DPLQREHQ]\ODWHG0DQQLFKEDVHVRI S\UD]LQDPLGH,QW-&KHP7HFK5HV 7KHDXWKRUVZRXOGOLNHWRWKDQNWKH3ULQFLSDO*RYW&ROOHJHRI 3KDUPDF\%DQJDORUHDQG'LUHFWRUDQG3ULQFLSDO1*60,36 &KDOXYDUDMX.&%KDW.,$PLQREHQ]\ODWHG0DQQLFKEDVHVRI DPLGHV 0DQJDORUHIRUSURYLGLQJWKHIDFLOLWLHVWRFDUU\RXWWKHUHVHDUFKZRUN -&KHP3KDUP6FL $MDL\HRED(22QRFKD3$2ODUHQZDMX27In-vitro anthelmintic properties of buchnolzia coriaceae and Gynandropsis gynandra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ite this article as: &KDOXYDUDMX .& %KDW ., 6WXGLHV RQ WKH DQWKHOPLQWLF -RVKL6.RVKDOD17LZDUL3In vitro study of some medicinally important SURSHUW\RIDPLQREHQ]\ODWHGPDQQLFKEDVHV-<RXQJ3KDUPDFLVWV 0DQQLFKEDVHVGHULYHGIURPDQWLWXEHUFXODUDJHQW%LRRUJ0HG&KHP Source of Support: Nil, ConÀict of Interest: None declared. Journal of Young Pharmacists Vol 3 / No 3 245.