Indian Journal of Chemistry Vol. 42B, August 2003, pp. 1937- 1942

Synthesis of indoloquinolones, triazoloindoloquinolines and its deri Yati yes

Y Y Mulwad* & M Y Lohar

Department of Chemistry. The Inst itute of Science. IS, Madam Cama Road. Mumbai 400032, India

Received 20 Aug List 2002; accepted (revised) I May 2003

I H.2H-2-0xo-4-hydrazinoquinolines la-e on treatment with cyc lohexanone give corresponding I H.2H-2-oxo-4-quinolinylcyc lohexanonehydrazones 2a-e. Thermal Fi scher indol izati on of 2a-e yield 5.6-d ihydro- 11 H -6-oxo- indoloI3.2-c]quinoline 3a-e. Chlorin ation of 3a-e affords the correspond ing chloro compounds II H-6-chloroi ndolo [3,2-c]quinolines 4a-e, which on treatment with hydrazine hydrate give IIH-6-indolo [3,2-c]quinoliny lhydrazines Sa-e. Thi s hydrazone is used as a building block to synthesize corresponding 3-chloro- I ' -( II H-indolor3.2-c]quinolin-6'y l-amino)-4-(4' -nitrophenyl) azetidin-2-ones 7a-e and l-pheny l-SH-indolo[3,2-c ]quinolin[3',4': 1,2] tri azoles Sa-e. la-e on treatment with p-nitrobenzaldehyde give 4-quinolinylhydrazono-I-4'-nitrophenyl methanes 9a-e, which on further treatment wi th chloroacetyl chloride in triethy l amine afford 3-chloro- 1 '-(4-quinolin-4'y l-amino)-4-(4'-nitropheny l)azetidin -2-ones lOa-e. Some of these compounds have been screened for their biologica l acti vity.

I H,2H-2-0xo-4-hydroxyquinolines and its 3-alkylated derivatives have a wide range of biological acti vities 1 such as antimic robial,2 antiasthma,3 antima­larial ,4 antiseptic,S hypnotic, sedative and CNS acti vi­ti es.6

.7 It is also synthetic precursor for many naturally

occurring quinoline8a and dimeric quinoline alka­loids. 8a

.b.c Azetidinone and triazole compounds are

known to possess broad spectrum of biological activi­ti es such as anti-tubercu losis, antiviral, CNS depres­sant, bactericidal , etc. From all the forgoing facts it was very interesting to sy nthesize a new series of azetidinone and tri azo le derivatives incorporated with quinolone moiety , which might possess some of the above potential medicinal app lications.

Our synthesis was initi ated by treatment of IH,2H-2-oxo-4-hydrazino-quinolines9 la-e with cyclohexa­none in acetic acid to afford I H,2H-2-oxo-4-quinolinyl cyclohexanonehydrazones 2a-e. The resulting hydra­zones were subjected to the thermal fi sher indolisation , followed by dehydrogenation to g ive the corresponding indoloquinolones 3a-e in the presence of pall ad ium on charcoal. These two reactions i.e. fi sher indolisation and aromatization were done in one-step. The struc­tures of these compounds were confirmed on the basis of their spectral data and e lemental analysis.

Ch lorination of 3a-e by using phosphorus oxych lo­ride and benzyltriethyl ammonium chloride afforded the corresponding chloro compounds 4a-e. Treatment of 4a-e with excess of hydrazine hydrate provided IIH-6-indolo[3,2-c]quino linylhydrazine Sa-e. The structures of these co mpounds were establi shed on the

bas is of their spectra l data and elemental analysis . Condensation of 5a-e with p-nitrobenzaldehyde af­forded the corresponding hydrazones 6a-e. Above compounds on treatment with chloroacetyl chl oride in

triethyl amine as a catalyst afforded 3-ch loro- 1 ' -(I I H­indolo[3,2-c ]quinolin-6' yl-amino )-4-( 4' -nitrophenyl)­azetidi n-2-ones 7a-e. ]n order to study structural ac­tivity relationship of compounds 7 and 10, la-e on treatment with p-nitrobenzaldehyde gave hydrazones 9a-e, which on further treatment with chl oroacetyl ch loride in triethyl amine as a catalyst affo rded 3-chl oro-l ' -( 6-methoxy-4-q uino l inA' -y I-ami no )-4-( 4' ­nitro phenyl) azetidin-2-ones 10a-e (Scheme I, Table I ). The structures of 10a-e are in agreement with their elemental analysis and spectral data.

Reaction of 5a-e with benzoyl chloride in HMPA yielded corresponding triazolo compounds, I-phenyl-

8H-indolo[3 ,2-c ]quinolin[3',4': 1 ,2] triazo les 8a-e. The structures of 8a-e are in agreement with their elemen­tal analysis and spectral data .

Experimental Section Melting po ints were taken in open capillari es and

are uncorrected. The IR spectra were recorded on a Perkin-Elmer 257 spectrophotometer using KB r, lH NMR and l3C NMR spectra in DMSO-d6 were recorded on VRX-300 and Bruker AMX-500 spec­trometers using TMS as internal standard and mass spectra on a Shimadzu. TLC ascertained the homoge­neity of the compounds on silica gel pl ates. The spots were developed in iod ine chamber.

1938 INDIAN J. CHEM., SEC B. AUGUST 2003

R' R'

~ N 0 o tx>R' ~

I Hydrazine hydr~e ~ ~ elhoxyelhano l ~

R 36 hr R '

cycJohexanon').

~ .l acelie aeid, r.I.R , 16 hr

I )Di phen yl elhe~58 ~ ~ .l 2)Pd/C 250 C. 1.5 hrs

2 N'HN=()

R'

R

R

OH

H I N' 0

~ 7

3 liN ;r-\, . I~ H HI 1,1

TEBA/P003 ~

48 hr

R

R'

p-nilro benzaldehydr

R 9

R'

R

o

R

R'

p-nilro del bcnZaldehYi

R'

)

o

4

NHN=CH-R" NHN-CH-R"

R" = PhNQz

Scheme I

J+CI o H

IH,2H-6-Methoxy-2-oxo-4-hydrazinoquinolines Ie. A mi xture of IH,2H-2-oxo-4-hydroxyquinoline (0.001 mole) , 2-ethoxyethanol (30 mL), and hydra­zine hydrate (15 mL) was refluxed for 36hr. The reac­tion mass was cooled to room temperature and the precipitate thus obtai ned was filtered , and recrystal­lised from ethanol.

IH, 2H-6-Methoxy-2-oxo-4-quinolinylcyclohexa­none hydrazone 2e. To a solution of 1 H , 2H-2-oxo-4-hydrazinoquinolines Ie (0.001 mole) in acetic acid (80 mL) was added a solution of cyclohexanone in

acetic acid (10 mL). The mixture was stirred at room temperature for 16hr, and the resulting precipitate ob­tained was fi ltered and recrystallised from ethano l.

5,6-Dihydro-IIH -2-methoxy-6-oxo-indolo[3,2-c]­quinoline 3e. The solution of 2e in d iphenyl ether was heated under reflux for 1 hr. The mixture was allowed to cool to lOOoe, and 10% palladium on charcoal (600 mg) suspended in diphenyl ether (20 mL) was added cautiously . The resulting mixture was heated under reflux for 1 hr. To the cold reaction mass hexane (l00 mL) was added. The resulting precipitate

MULWAD el 01.: SYNTHESIS OF INDOLOQUINOLONES & TRIAZOLOINDOLOQUINOLINES 1939

Table I-Characteri za tion data of the compounds prepared

Compd R R' Mol. formula* Ill.p. Yield °C (0/0)

la H H C<)H9N)0 262 75 Ib CH] H C\OH11N,0 >260 5R Ic H CH, C\OH 11 N3O 25R 62 Id OCH3 H C IOH 11N)0 2 >260 65 Ie H OCH, C\OH 11 N10 2 >260 7R 2a H H C1sH 17N1O 232 75 2b CH) H C 16H 19N,0 218 66 2c H CH) Cl6Hl9N30 224 62 2d OCH3 H C I6H I9N)02 243 70 2e H OCH) CI6H I9N)02 >260 65 3a H H C1sH \ON2O 243 72 3b CH] H Cl6Hl2N20 201 62 3c H CH) Cl6Hl 2N20 189 67 3d OCH3 H Cl6Hl 2N20 2 224 67 3e H OCH1 Cl6Hl 2N20 2 >260 56 4a H H C 1sH9N2Ci 226 98 4b CH, H Cl6HI IN2Ci 237 98 4c H CH) Cl6HIIN2Ci 218 96 4d OCH] H Cl6HIIN2CiO 247 98 4e H OCH) Cl6HIIN2CiO 252 95 Sa H H ClsHl 2N4 167 56 Sb CH) H ClhHl4N4 146 50 Sc H CH] Cl6Hl4N4 183 47 Sd OCH) H Cl6Hl4N40 174 56 Se H OCH1 ClhHl4N40 193 45 6a H H Cn Hl sNs02 204 73 6b CH) H C2:1H 17Ns0 2 214 64

6c H CH] C2]H 17Ns0 2 193 74 6d OCH) H C23H 17NsO] 178 72 6e H OCH J C23H 17NsO) 169 54 7a H H C24Hl6Ns0 2Ci 209 73 7b CH) H C25HIRNs03Ci 223 64

7c H CH J C2sH lxNsO,Ci 219 71 7d OCH) H C2sH 1 xN 50 4CI 232 67 7e H OCH] C25H 1 xN 50 4Ci 228 54 8a H H Cn H l4N4 218 53 8b CH1 H C2,H 16N4 205 58 8c H CH) C2:1H lhN4 182 48 8d OCH) H C2)H I6N4O 168 42 8e H OCH) C23Hl6N40 175 38 9a H H C 16H12N40] 187 65 9b CH) H C 17H I4N4O] 210 71 9c H CH1 C 17HI4N4O] 172 74 9d OCH, H Cl 7Hl4N404 196 78

-Camel

1940 INDIAN J. CHEM ., SEC B, AUGUST 2003

Table I- Characteri za tion data of the compounds prepared- Conld

Compd R R' Mol. formul a* m.p. Yield

°c (%)

ge H OCH 3 C17HI4N40 4 224 65

lOa H H Cl xH IJN40 4Ci 2 13 56

lOb CH1 H CI9HI SN40 4Ci 202 45

IOc H CH, ClyHI SN404Ci 181 49

IOd OCHJ H CI <)H IsN4O,Ci 173 52

IOc H OCH 3 C I<) H 15N4OsCI 162 57

Ie : IR(cm' I): 3468, 3356, 3297 (N-H str.), 1642 (CO; amide): IH NMR (DMSO-dl\): I) 3.8 (s, 3H, OCHJ). 4.28 (br. s, 2H . NH2,), 5.70 (s, I H. C, ). 7.06 (d, I H, C7, J=7Hz), 7. 15 (d. I H.Cx, J=8 Hz), 7.4 (s, I H, Cs), 8. 12 (s, I H,NH. D20 exchangeable), I) 10.58 (s, I H. H. D20 exchangeable): IJC NMR: I) 55.57(OCH,). 90.62(C1) , 104. 18 to 122.83 (aromatic carbons), I 33(Cxa), 148.37(C4), 153.8(Cn) and I 63.07(C2) : MS: mlz 205 ( 100%). 190, 172, 162. 146, 133, 11 7, 104,9 1, etc.

2e: IR(cml): 3435, 3340 (N-H str.) , 2985, 2896, 1639 (CO: amide), 1604: IH NMR (DMSO-dl\): I) 1.64 - 1.69 (m, 2H. C4'). 2.34 - 2.37 (m. 4H. C1, and Cy ) , 2.50 - 2.55 (m, 4H. C~, and C6' ), 3.8(s, 3H, OCH3), 6.04 (s, I H, CJ), 7. 14 (d , I H, C7, J=8Hz), 7, 19 (d, I H. cx, J=8Hz) , 7.45 (5, I H, Cs). 9. 16 (s, I H, H, D20 exchangeable) and 10.82 (s. I H. NH. D20 exchangeable); IJ C MR: I) 25.19tC4} 25 .73 (Cy ) . 26.93 (Cy ), 27.27 (C2'). 35 ,23 (Cn,). 55.68 (OCH,), 104 to 123.2 (aromatic carbons), 137. 1 (CXa), 149. 16(C4), 156.3 (CI'). 159.8(Cn), andlo2.3(C2); .MS: mlz 285 (100%). 270, 256, 242. 229, 2 17, 20 1. 189. 175, 162, 146. 132, 11 8. 104,91 , etc.

3e: IR(cm' I): 3374. 32 10 (N-H str. ), 2992. 2834, 1639 (CO; amide), 16 10: IH NMR (DMSO-dl\) : I) (s, 3H. OCH,) 7.17 (d, I H.C7.J=8Hz), 7.25- 7.28 (dd, 2H. Ar.), 7.4- 7.56 (dd, 2H. ArH), 7.63 (d, I H.CJ, J=8Hz), 7.79 (s . I H,CI). 8.2 (d. I H,C4. J=8Hz), I i .29 (s, I H. NH, 0 20 cxchangeable), 12.5 (s, IH , NH. D20 exchangeable): I3C NMR : I) 55.45 (OCH, ), 109.04 to 124.38 (aromat ic carbons), 132.27 (C ma), I:l7.6(C4a), 140.56 (C II ,,) , 154.06 (C2) and 159.45 (Cr,): MS : mlz 264,249. 235, 22 1 ( 100 %), 192. 164, 140, 11 3.97, 87. etc .

4c: IR(cm,I): 3327 ( -H str.), 1648 (C=N), 1619: I H NMR (DMSO-dr,) : I) 367(s, 3H, OCHJ) 7. 12 (d, I H,C7.J=8Hz), 7.25, 7.28 (dd, 2H, ArH). 7.4, 7.56 (dd, 2H, Ar.). 7.63 (d, I H,C3.J=8Hz) , 7.79 (5.1 H,CI). 8.2 (d,1 H,C4.J=8Hz), I 1.29(s, I H, H,D20 exchangeable). 12.5 (s, I H. H. D~O exchangeable): IJCMR : I) 55.45(OCH) , I 05. 14 to 123.6 (aromatic carbons), 132.89 (C Wa), 139.2 C4al , 142.29 Clla), 155.04 Cn) and 162.45 (C2) : MS: mlz: 284(M+\ 282(M+) , 249, 235, 22 1 (100 %), 192, 164. 140. I 13, 97, 87, etc.

Se: IR (cm' I): 3453, 3346 and 3289 (N- H str. ). 1645(C=N), 1610: IH NMR (DMSO-dil) : I) 3.66 (s. 3H, OCH,), 4.4 (br. s, 2H, NH 2), 7.3 (d, III. C7• J=8Hz). 7.36 (d, I H. Ar-H. J=7Hz), 7.5 (m, I H, Ar-H), 7.6 (d, I H, Ar-H, J=8Hz), 7.74 (d, I H, J=8Hz), 8.02 (d . I H. C,' J=8Hz), 8.3 (d. I H, C4. J=8Hz) , 10.57 (s. I H, NH . D20 exchangeable), 12.6 (5 , I H.NH,D20 exchangeable); I' C NM R: I) 55.48 (OCH,), 105. 14 to 126.4 (aromatic carbons), 133 .68 (C 10,,)' I 38.4(C4,,). 140.13 (C Ila). 155 .04 (Cn) and 161.86 (C l ) .

6e: I R(cm,I): 3435. 3340 (N-H str. ), 2982, 1639 (C=N), 1604. 1568; I H NMR (DMSO- dil ): I) 3.78 (s. 3H. OCH,), 6.9 (s. I H, Ar-H). 7.25 (d. I H. C). J=8Hz), 7.36 (d, I H, Ar-H . J=8Hz) , 7.43 (m, I H. Ar-H). 7.63 (dd, I H, Ar-H), 7.7 1 (d, I H, Ar-H, J=8Hz), 8.0 1 (d , I H. Ar-H. J=8Hz) . 8. 1 (d. I H, C4, J=RHz), 8.2 (s , I H. C I), 9.8 (s, I H, NH, D20 exchangeable), I) 11 .3 (s, I H, NH. D10 exchangeable): I.1CNM R: I) 56.6 (OCH,), 106 to 128.73 (aromati c carbons), 131.72, 135.7 (C IO,, ) , 138.5 (C4a), 141 (C lla), 146.2 (C,·), 153.05 (Cn) and I 63.03(C2).

7e: II« cm'\ 34 16. 3320 ( -H str. ). 1730(C=0),I64 I (C=N), 155 1; IH NMR (DMSO-dl\): I) 2.6(d. IH , CH-Ph, J=7.2 Hz). 3.7 (d, IH. CH-CI, J=6.0 Hz), 3.8 (s, 3H. OCH1) , 7.2 (s . I H, Ar-H), 7.4 (d, I H, Ar-H, J=8Hz), 7.5 (d , I H, C). J=8Hz), 7.65 (m, 2H, Ar-H). I) 7.R (dd, I H, Ar-H). 7.9 (d, I H, Ar-H, J=8Hz), 8. 1 (d. I H, Ar-H, J=8Hz), 8.2 (d. I H, C4 , J=8Hz), 8.3 (s, I H, CI), 10.3 (s, I H, NH). 11.9 (s, I H, NH): I.1C NMR: I) 27(C4), 56.8 (OCH,), 93(C1) , 108 to 128.36 (aromatic carbons), 133 .1 (C w'), 137.32 (C4·,.), 142.27 (C II ·a). 153. 13 (Cn'),

I 59.45(C2') and I 72(C l ) .: MS: mlz: 489(M+\ 487(M+), 452, 424, 406, 378, 364. 350, 322, 245. 2 15, 202, 190, 176. 150. etc.

Re: IR(cm,I): 34 16,3320 (N-H str. ), 2982, I 656(C=N). 1604, 155 1: IH NMR (DMSO- dil): I) 3.7 (s. 3H, OCH) , 7. 1 (d, IH. Ar-H . .I=RHz) , 7.2 (d. I H. Ar-H. J=8Hz), 7.3 (m. 2H, Ar-H), 7.5 (d, I H. CI h .I=8Hz), 7.6 (dd. I H. Ar-H), 7.8 (d, I H, Ar-H. J=8Hz). 7.9 (m, 2H, Ar-H). 8.2 (d. I H, C11, J=8Hz) . 8.3 (s, I H. Cy ) . 11.3 (s, I H. NH, D20 exchangeable): I3C NMR: I) 56.8 (OCH1), 107 to 127.47 (aromatic ca rbons), 133. 1 (C w·). 137 .32 (el 'a) ' 142.27 (C II 'a), 153. 13 (C(; ) and I 59.45(C2').

ge: IR(cm·I): 3416, 3320 (N-H str.). 2982. 1730(C=0), I 632(C=0), 1604. 1551 : IH NMR (DMSO-dr,): I) 3.78 (s, 3H. OCH,). 6.4 (s. IH , CJ), 6.9 (s. I H, Ar-H), 7.25 (d, I H, C7, J=8Hz). 7.36 (d, I H, Ar-H. J=8Hz). 7.43 (d, I H, Ar-H. J=8Hz). 7.63 (d, I H. Ar-H, J=7 Hz), 7.71 (d, I H. Ar-H, J=8Hz), 8.0 I (d. I H, Ar-H. J=8Hz), 8. 1 (d, I H, CR, .I=8Hz), 8.2 (s, I H, Cs), I) 9.5 (5, I H, H, D20 exchangeable). I) 11 .2 (s. I H. H, D20 exchangeable) : IJC NMR: I) 56.6(OCH1), 103 to 125 .27(aromatic carbons), 143. 1 (C,·), I 56.7(C6 ) and 162.46 (C2).

lOe: IR(cm,I): 3435, 3340 ( -H st r.). 2982, 1734 (C=O). 1639 (C=O: amide), 1547; IH NMR (DMSO-dl\): I) 2.62 (d . I H. CH-Ph, J=7.2 Hz). 3.72 (d, I H, CH-Ci . .1=6.0 Hz), 3.R2 (s. 3H, OCH1). 6.4 (s, I . C)· ). 7.2 (d, I H, Ar-H . .I=8Hz), 7.5 (d , I H, CT , .I=8Hz). 7.65 (m. 2H, Ar-H). 7.8 (d. I H. Ar-I-1. .I=8Hz). 8. 1 (d. I H. Ar-H, J=R Hz) , 8.2 (d, I H. Cwo J=8Hz) . 8.3 (s. I H, C,, ), 9.8 (s. I H, H. D20 exchangeable). 11.2 (s . IH. NH. D20 exchangeable): IJC NMR: I) 26.43(C4). S6.5(OCH), 96 (Cl ), 105.4 to 127 (aromatic ca r ons) . 136.72 (C4').

14 1.67(Cx'a). 158.53 (C(,) and 170. 12(C2); MS: mlz: 4 Io(M+\ 4 14(M+). 379. 35 1. 333. 305. 291. 277 . 249, 172, 162. 146, 133 . 117. 104, () I etc.

" A ll the above compoLinds gave sati sfactory elemental ana lysis

MULWAD et al.: SYNTHESIS OF INDOLOQUINOLONES & TRIAZOLOINDOLOQUINOLINES 1941

was filtered and washed with hexane (2x50 mL). It was taken up in boiling 2-ethoxyethanol and filtered for the elimination of palladi zed charcoal, and the solvent was evaporated under reduced pressure. The solid thus obtained was recrystallised from ethanol.

11H -6-Chloro-2-methoxyindolo[3,2-c ]quinoline 4e. A mixture of 3e (0.00 1 mole), acetonitrile (20 mL), benzy ltriethylammonium chloride (l.45g, 0.0064 moles) , diethylaniline ( lmL) and phosphorus oxychloride (7 .5 mL, 80 minol) was heated at reflux for 48 hr and evaporated under reduced pressure. Ice ( 100 g) was added to the residue. The sticky mass obtained was stirred at room temperature and the re­sultant solid was filtered , suspended in water (50 mL) and treated with excess ammonia (25 mL), and the solid thus obtained after stirring at room temperature for 2hr, was filtered , washed with water, dried and crysta lli zed from ethano l.

11H -2-Methoxy-6-indolo[3,2-c ]quinolinylhydra­zine Se. The mi xture of 4e (0.00 1 mole) and hydra­zine hydrate (80 mL) was refl uxed for 48hr. The reac­tion mass was cooled to room temperature and the precipitate obtained was filtered, and recrystallised fro m ethanol.

llH -2-Methoxy-6-indolo[3,2-c ]quinolinylhydra­zono-1-4'-nitrophenylmethane 6e. To a solution of 5e (0 .00 1 mole) in acetic ac id (40 mL) was added a sol ution of p-nitrobenzaldehyde (2gs). The mi xture was stirred at room temperature for 10hr, and the re­sulting precipitate was filtered, washed with ethanol, and dried to give 6e.

3-Chloro-1'-(llH-2'-methoxyindolo[3,2-c ]quino­Iin-6'-yl-amino )-4-4'-nitrophenyl azetidin-2-one 7e. Compound 6e (0.001 mole) was dissolved in dioxane (35mL) and to this soluti on; chloroacetyl chloride (0.00 1 mole) and triethylamine (0.00 1 mole) were added. Then the reacti on mixture was refl uxed for 12hr. At the end of the reaction the solvent was re­moved in vacuo and res idue was poured into 50 mL iced-water. The preci pitate thu s obtained was filtered off, washed with water, dri ed and crystalli zed from ethano l.

1 0-Methoxy-l-phenyl-8H -indolo[3,2-c ]quinolin­[3', 4': 1,2]triazoles 8e. To a mi xture of Se (0.00 1 mole) and HMPA (20mL), benzoyl chloride (0.00 1 mole) was added slowly in 10 min . The resultant mix­ture was heated first at 85°C for Ihr. Subsequently the temperature was raised further to 220°C and heated at this temperature for 4 hr. The reac tion mass was then cooled to room temperature and poured on 50 mL

iced-water. The resulting precipitated compound was filtered off, washed with water, dried and crystallized from ethanol to give 8e.

6-Methoxy-4-quinolinylhydrazono-1-4' -nitrophe­nylmethane ge. To a solution of Ie (0.00 1 mole) in acetic acid (40) was added a solution of p­nitrobenzaldehyde (2gs) . The mixture was stirred at room temperature for IOhr, and the resulting precipitate was filtered , washed with ethanol , and dried to give ge.

3-Chloro-l' -( 6-methoxy-4-quinolin-4' yl-amino )-4-4'-nitrophenylazetidin-2-one lOe. Compound ge (O.OOlmole) was dissolved in dioxane (35mL) and to this solution; chloroacetyl chloride (0.00 1 mole) and triethylamine (0.00 1 mole) were added. Then the reaction mixture was refluxed for 12hr. At the end of the reaction the solvent was removed under vacuum and the residue was poured into 50 mL iced water. The resulting precipitated compound was filtered off, washed with water, dried and crystallized fro m ethanol.

Biological screening Antibacterial activity

Compounds 7a, 7b, 7c, lOa, lOb and 10c from the series were screened for their antibacterial acti vity (Table II) against both Gram-positive and Gram­negative bacteri a. The minimum inhibitory concentra­tion (MIC) of these compounds was determined by the tube dilution method. 1o Cephalosporin was em­ployed as the standard drug and DMF as a standard.

Table II- Biologica l screening results of compounds 7a, 7b, 7e , lOa, lOb and 10e (MIC in J,.lg/mL).

Compd Streptococcus aureus Salmonella typhi

7a +++ +++

7b ++ +

7e + +

lOa +++ +++

lOb ++ ++

lOe ++ +

Std * ** 200 J,.lgm/mL = +, 150 J,.lgm/mL =++, 100 J,.lgm/mL = +++, 50 J,.lgrn/mL = ++++, not act ive = -, * = 8J,.lgIll/IllL, ** = 10J,.lgrn/lllL.

Acknowledgement.

The authors are thankful to Mr Chipul an kar, MUlCT, Mumbai for e lemental analys is. The Director TIFR , and RSIC, Mumbai for IH NMR, 13C NMR and mass spectra respectively. The authors are also

1942 [ND[AN J. CHEM ., SEC B, AUGUST 2003

thankful to the Haffkine Institute, Mumbai for biological screening.

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