Neelam Bharti

Anti-inflammatory, analgesic and antiamoebic activity evaluation of pyrimido[1,6-a]benzimidazole derivatives synthesized by the reaction of ketoisothiocyanates with mono and diamines.

(UN) substituted o-phenylenediamines 1a-g reacted with 3-isothiocyanatobutanal to give pyrimidobenzimidazole derivatives, 2a-g, respectively. Products 4, 6 and 8, 10 were obtained by condensation of 3-isothiocyanatobutanal with 2,3-diaminopyridine, 1,4-diaminobutane and 3-isothiocyanatopropanal with 4,5-dimethyl-1,2-phenylenediamine, o-nitroaniline, respectively. S-Methylation of 2f and 11b gave products 12a and 12b, respectively. Anti-inflammatory and analgesic activity evaluations of 2a-g and 12b were carried out at 50 mg kg(-1) p.o. Compound 2c exhibited good anti-inflammatory (46%) and mild analgesic activity (50%). Antiamoebic activity evaluations (using microdilution method) of 2a-g against Entamoeba-histolytica (strain HM1: IMSS) were carried out and compounds 2a, 2b, 2d and 2g exhibited good antiamoebic activity in vitro.

Synthesis and in vitro antiprotozoal activity of 5-nitrothiophene-2-carboxaldehyde thiosemicarbazone derivatives

Several thiosemicarbazone derivatives of 5-nitrothiophene-2-carboxaldehyde were prepared by the simple process in which N(4)-thiosemicarbazone moiety was replaced by aliphatic, arylic and cyclic amine. Among these thiosemicarbazones compound 11 showed significant antiamoebic activity whereas compound 3 was more active antitrichomonal than the reference drug.

New palladium(II) complexes of 5-nitrothiophene-2-carboxaldehyde thiosemicarbazones: synthesis, spectral studies and In vitro anti-Amoebic activity

Thiosemicarbazones (1-7) and their palladium(II) complexes (1a-7a) of the type [Pd(TSCN)Cl(2)] (where TSCN=thiosemicarbazone) were prepared from 5-nitro thiophene-2-carboxaldehyde and [Pd(DMSO)(2)Cl(2)], respectively. Coordination via the thionic sulphur and the azomethine nitrogen atom of the thiosemicarbazones to the metal ion were confirmed by spectral data. These compounds were screened in vitro against (HK-9) strain of Entamoeba histolytica possess amoebicidal properties. Enhancement of antiamoebic activity resulted due to the introduction of palladium metal in the thiosemicarbazone moiety. The most promising of the group tested are [Pd(5-N-2-TCA-COTSCN)Cl(2)] and [Pd(5-N-2-TCA-AdmTSCN)Cl(2)] comparable to that of metronidazole.

Synthesis and antiamoebic activity of new cyclooctadiene ruthenium(II) complexes with 2-acetylpyridine and benzimidazole derivatives.

Reaction of [Ru(eta4-C8H12) (CH3CN)2 Cl2] with 2-(2-pyridyl) benzimidazole or Schiff bases derived from 2-acetylpyridine and S-methyldithiocarbazate, S-benzyldithiocarbazate and thiosemicarbazide leads to form new complexes of the type [Ru(eta4-C8H12)(L)Cl2] (where L=ligand). In vitro, most of the compounds exhibited potent activity and the Ru derivatives 1a [Ru(eta4-C8H12)(2-Acpy-SMDT)Cl2], 2a [Ru(eta4-C8H12)(2-Acpy-SBDT)Cl2] and 3a [Ru(eta4-CsH12)(2-Acpy-TSC)Cl2] were found more active than metronidazole against (HK-9) strain of Entamoeba histolytica.

Synthesis, characterization and antiamoebic activity of benzimidazole derivatives and their vanadium and molybdenum complexes.

Reaction of [MoO(2)(acac)(2)] (where, acac=acetyl acetone) and KVO(3) with 2-(salicylidieneimine) benzimidazole lead to form new complexes [MoO(2)(sal-BMZ)(2)] and K [VO(2)(sal-BMZ)(2)] [where, sal-BMZ=2-(salicylidieneimine) benzimidazole], which showed the monobasic bidentate nature of the ligand in which the phenolic oxygen and the imine nitrogen of the ligand are coordinated to the metal ion. These complexes were characterized along with nine other complexes of oxoperoxovanadium (V), molybdenum (Vl) and tungsten (Vl) with benzimidazole derivatives and screened in vitro by micro dilution technique for their amoebicidal activity with a view to search for a more effective agent against Entamoeba histolytica suggests that compound 2 and 3 might be endowed with important antiamoebic properties since they showed IC(50 )values in a microM range.

Synthesis, characterisation and antiamoebic activity of new thiophene-2-carboxaldehyde thiosemicarbazone derivatives and Their cyclooctadiene Ru(II) complexes

Reaction of new thiosemicarbazones (1-4) derived from thiophene-2-carboxaldehyde and cycloalkylaminothiocarbonylhydrazine with [Ru(eta(4)-C8H12)(CH3CN)2Cl2] leads to form complexes (1a-4a) of the type [Ru(eta(4)-C8H12)(TSC)Cl2] (where TSC=thiosemicarbazone). All the compounds have been characterised by elemental analysis, IR, 1H NMR, electronic spectra and thermogravimetric analysis. It is concluded that the thionic sulphur and the azomethine nitrogen atom of the ligands are bonded to the metal ion. In vitro antiamoebic screening against (HK-9) strain of Entamoeba histolytica indicated that the Ru(II) complexes of thiophene-2-carboxaldehyde thiosemicarbazones were found more active than the thiosemicarbazones.

Synthesis, thermal and spectral studies of oxoperoxo and dioxo complexes of vanadium(V), molybdenum(VI) and tungsten(VI) with 2-(α-hydroxyalkyl/aryl)benzimidazole

Reaction of 2-(α-hydroxymethyl)benzimidazole or 2-(α-hydroxyethyl)benzimidazole (LH) with the peroxovanadium(V) species, generated in situ by stirring V2O5, KOH and 30% aqueous H2O2, gives the corresponding complexes of formula K[VO(O2)L2]. Similar peroxo species of molybdenum and tungsten generated by stirring MoO3 or WO3·H2O with an excess of 30% aqueous H2O2 readily react with 2-(α-hydroxyethyl) benzimidazole in aqueous EtOH to give the peroxo complexes [MO(O2)L2] (M=Mo or W). The dioxo complexes of general formula [MO2L2] have also been isolated by the reaction of [MoO2(acac)2] or [WO2- (acac)2] (acacH=acetylacetone) with the above ligands and with 2-(α-hydroxybenzyl)benzimidazole. The dioxo complexes are white, whereas peroxo complexes are light yellow to orange. The peroxo complexes generally decompose in two steps: (i) the decomposition of the peroxo group and (ii) the decomposition of the alkyl/aryl group followed by decomposition of the complete ligand. On the other hand, decomposition of the dioxo complexes follows only in a later step. All the peroxo complexes exhibit three i.r. active vibrational modes at ca. 860u2009cm−1, 760u2009cm−1 and 600cm−1, characteristic of the η2-coordinated peroxo group. The dioxo complexes are dominated by the presence of two sharp bands in the 900u2009cm−1 region due to νsym(O=M=O) and νasym(O=M=O) modes. The ν(C=N) (ring) and ν(OH) shifts have also been measured in order to locate the coordination sites of the ligands. A broad band at ca. 400u2009nm in the peroxovanadium(V) complexes, while the absorption at ca. 350u2009nm in the peroxomolybdenum(VI) and tungsten(VI) complexes is assigned to the peroxo-metal charge transfer band.

Synthesis, crystal structure, and enhancement of the efficacy of metronidazole against Entamoeba histolytica by complexation with palladium(II), platinum(II), or copper(II)

Reaction of trans-[PdCl2(DMSO)(2)]. cis-[PtCl2(DMSO)(2)]. and [Cu(OAc)(2)](H2O)-H-. with metronidazole (mnz) leads to the formation of new complexes, i.e., trans-[PdCl2(mnz)(2)] (1), trans-[PtCl2(mnz)(2)] (2). and trans-[Cu-2(OAc)(4)(mnz)(2)] (3), respectively. Complexes 1-3 crystallize all in the centrosymmetric monoclinic space group P2(1)/c with Z = 8. Unit-cell parameters for these complexes are: 1, a = 7.1328(14) Angstrom, b = 20.699(4) Angstrom, c = 7.1455(14) Angstrom, and beta = 116.17(3)degrees; 2, a = 9.9169(14) Angstrom, b = 21.853(4) Angstrom, c = 6.7218(13) Angstrom, and beta = 110.79(3)degrees: 3. a = 9.1663(18) Angstrom, b = 19.129(4) Angstrom, c = 8.9446(18) Angstrom, and beta = 116.44(3)degrees. The complexes 1 and 2 maintain an ideal square-planar geometry. In complex 3, the H2O molecules of the starting complex are replaced by metronidazole while maintaining a dimeric structure of [Cu(OAc)(2)]. Each Cu ion has an ideal octahedral structure, though distortion occurs in the equatorial position where the acetato ligands are attached. The Cu-Cu separation of 2.6343(8) Angstrom indicates considerable metal-metal interaction. The testing of the antiamoebic activity of these complexes against the protozoan parasite Entamoeba histolytica suggests that compound 1-3 might be endowed with important antiamoebic properties since they showed IC50 values in a muM range better than metronidazole (Table 2). Thus, compound 1 displayed more effective amoebicidal activity than metronidazole (IC50 values of 0.103 muM vs. 1.50 muM resp.).

Synthesis, characterization, and screening for antiamoebic activity of Palladium(II), Platinum(II), and Ruthenium(II) complexes with NS-donor ligands

Reaction of [PdCl2(DMSO)2], [PtCl2(DMSO)2], and [RuCl2(η4-C8H12)(MeCN)2] with S-acetyl Nβ-acetyldithiocarbazate (=2-acetylhydrazinecarbodithioic acid anhydrosulfide with ethanethioic acid; aadt; 1), S-methyl Nβ-[(5-nitrothiophene-2-yl)methylene]dithiocarbazate (=S-methyl 2-[(5-nitrothiophene-2-yl)methylene]hydrazinecarbodithioate; mntdt; 2), and S-benzyl Nβ-[(5-nitrothiophene-2-yl)methylene]dithiocarbazate (=S-benzyl 2-[(5-nitrothiophene-2-yl)methylene]hydrazinecarbodithioate; bntdt; 3) led to new complexes [PdCl2(L)], [PtCl2(L)], and [RuCl2(η4-C8H12)(L)] (L=ligands 1–3). All these compounds were characterized by elemental analysis, IR, 1H- and 13C-NMR and UV/VIS spectra and thermogravimetric analysis. Ligand 1 coordinates through the thioxo S-atom and the carbazate N(β) atom, whereas in ligands 2 and 3 the thioxo S-atom and the azomethine N-atom are coordinated to the metal ion. Screening of antiamoebic activity of these compounds was performed in vitro against the HK-9 strain of E. histolytica. All the complexes were more active than their respective ligands; compound 3a showed the most promising activity.