Kishwar Saleem

Platinum Compounds: A Hope for Future Cancer Chemotherapy.

The discovery of cis-platin and its second and third generation analogues created a hope in cancer chemotherapy. Cis-platin and its second generation analogue carboplatin have been used for the treatment of some cancers from a long time. The third generation analogues have superior anti-cancer profiles for curing a few cancers. Unfortunately, certain side effects such as renal impairment, neurotoxicity and ototoxicity etc. are associated with these drugs. But, combination therapy makes these analogues more effective with fewer side effects. In addition, the results of some ongoing clinical trials will make the safety profile clear in near future. The present article describes the current status of cis-platin and its analogues in cancer chemotherapy. In addition, special emphasis has been made on cis-platin discovery, development of second (carboplatin, oxaliplatin, nedaplatin) and third (lobaplatin, heptalatin) generation analogues, comparison of their chemotherapies, mechanism of action, therapeutic status, recent developments and chronology. Moreover, attempts have been made to describe the future perspectives of these drugs in the cancer treatment.

Polysaccharides Chiral Stationary Phases in Liquid Chromatography

Chiral resolution has achieved an independent identity in the separation sciences and polysaccharide CSPs are viewed as effective and efficient CSPs due to their many unique advantages. The present review article highlights the separations of chiral pharmaceuticals and drugs by liquid chromatographic modalities (high performance liquid chromatography, capillary electro‐chromatography, sub‐ and super critical fluid chromatography and thin layer chromatography) utilizing polysaccharide CSPs. Enantiomeric resolution at analytical and preparative scales and a comparison of coated and immobilized CSPs is discussed. The optimization strategies for enantiomeric separation have also been presented. The possible mechanisms of chiral resolution of racemates were also included. The commercial CSPs of all the Companies i.e., Daicel, Kromasil, Macherey Nagel, Knauer and Sepaserve have been compared and discussed. Finally, the role of these CSPs in chiral drugs development programs has also been identified.

Curcumin-I Knoevenagel's condensates and their Schiff's bases as anticancer agents: synthesis, pharmacological and simulation studies.

Pyrazolealdehydes (4a-d), Knoevenagels condensates (5a-d) and Schiffs bases (6a-d) of curcumin-I were synthesized, purified and characterized. Hemolysis assays, cell line activities, DNA bindings and docking studies were carried out. These compounds were lesser hemolytic than standard drug doxorubicin. Minimum cell viability (MCF-7; wild) observed was 59% (1.0 μg/mL) whereas the DNA binding constants ranged from 1.4×10(3) to 8.1×10(5) M(-1). The docking energies varied from -7.30 to -13.4 kcal/mol. It has been observed that DNA-compound adducts were stabilized by three governing forces (Van der Walls, H-bonding and electrostatic attractions). It has also been observed that compounds 4a-d preferred to enter minor groove while 5a-d and 6a-d interacted with major grooves of DNA. The anticancer activities of the reported compounds might be due to their interactions with DNA. These results indicated the bright future of the reported compounds as anticancer agents.

Synthesis and in vitro antibacterial activity of new steroidal thiosemicarbazone derivatives

We investigated the antibacterial activity of some new steroidal thiosemicarbazone derivatives, prepared from the reaction of cholest-5-en-7-one with thiosemicarbazides, in ethanol in the presence of a few drops of HCl at 80 degrees C in high yield. All the compounds have been characterized by means of elemental analyses, IR, 1H NMR and mass spectroscopic data, to find an effective antibacterial agent. The antibacterial activity was first tested in vitro by the disk diffusion assay against two Gram-positive and two Gram-negative bacteria, and then the minimum inhibitory concentration (MIC) of compounds was determined. The results showed that the steroidal thiosemicarbazones derivatives inhibit growth of both types of the bacteria (Gram-positive and Gram-negative). The acetoxy and chloro derivatives of cyclopentyl and cyclohexyl amine thiosemicarbazones were found to have more antibacterial activity than the other derivatives.

Synthesis, characterization and in vitro antibacterial activity of thiourea and urea derivatives of steroids.

Some heterocyclic systems namely stigmest-6-en-7, 5alpha thiourea and stigmest-6-en-7, 5alpha urea derivatives of steroids were synthesized by the reaction of stigmest-5-en-7 one with thiourea/urea in the presence of a few drops of conc. HCl at 80 degrees C in high yield. All the compounds have been characterized by means of elemental analyses, IR, 1H NMR, 13C NMR and mass spectroscopic data. The antibacterial activity was first tested in vitro by the disk diffusion assay against two Gram-positive and two Gram-negative bacteria, and then the minimum inhibitory concentration (MIC) of compounds were determined. The results showed that steroidal thiourea derivatives inhibit growth as compared to steroidal urea derivatives of both type of the bacteria (Gram-positive and Gram-negative). Compounds 3 and 4 are better antibacterial agents as compared to standard drug chloramphenicol.

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, DNA binding, hemolysis assays and anticancer studies of copper(II), nickel(II) and iron(III) complexes of a pyrazoline-based ligand

BACKGROUND Over the last few decades, metal-based drugs, particularly cisplatin and its analogs have been used for the treatment of various cancers. Currently, scientists are developing other metal complexes as anticancer agents to eliminate the toxicity associated with platinum drugs. RESULTS Claisen-Schmidt condensation was used to synthesize the pyrazoline-based ligand; (5-(4-chlorophenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide), followed by the synthesis of its complexes with copper(II), nickel(II) and iron(III) metal ions. DNA binding and in silico studies indicated quite good binding with DNA; requirements for good anticancer drugs. CONCLUSION DNA binding constants for ligand, copper, nickel and iron complexes were 1.42 × 10(4), 3.16 × 10(4), 5.82 × 10(5) and 6.72 × 10(5) M(-1), respectively, indicating strong binding with DNA. All the reported compounds were slightly hemolytic towards rabbit red blood corpuscles and exhibited moderate activities against MCF-7 cancer cell lines.

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 and synergistic antifungal activities of a pyrazoline based ligand and its copper(II) and nickel(II) complexes with conventional antifungals

A pyrazoline based ligand; (5-(4-chlorophenyl)-3-phenyl-4, 5-dihydro-1H-pyrazole-1-carbothioamide) has been synthesized by Claisen-Schmidt condensation of acetophenone with p-chlorobenzaldehyde, followed by sodium hydroxide assisted cyclization of the resulting chalcone with thiosemicarbazide. Metal ion complexes of the synthesized ligand were prepared with Cu(II) and Ni(II) metal ions, separately and respectively. Ligand and the metal complexes were characterized by elemental analysis, FT-IR, UV-Vis, (1)HNMR, ESI-MS and (13)CNMR spectroscopic techniques. Molar conductance measurements in DMSO suggested non-electrolytic nature of the complexes. Tetragonally distorted octahedral geometry for copper and octahedral geometry for the nickel complexes was proposed on the basis of UV-Vis spectroscopic studies and magnetic moment measurements. The complexes were investigated for their ability to kill human fungal pathogen Candida by determining MICs (Minimum inhibitory concentrations), inhibition in solid media and ability to produce a possible synergism with conventional most clinically practiced antifungals by disc diffusion assay and FICI (fractional inhibitory concentration index).

Chiral separations of some β-adrenergic agonists and antagonists on AmyCoat column by HPLC

Sixteen beta-adrenergic antagonists namely acebutalol, alprenolol, atenolol, bisoprolol, bopindolol, bufurolol, carazolol, celiprolol, indenolol, metaprolol, nebivolol, oxprenolol, practolol, propranolol, tertalol, and timolol, and two beta-adrenergic agonists namely cimeterol and clenbuterol were resolved on AmyCoat (150 x 46 mm, 3 microm size of silica particle) by using (85:15:0.1, v/v/v), (90:10:0.1, v/v/v), and (95:05:0.1, v/v/v) combinations of n-heptane, ethanol, and diethylamine solvents, respectively. The flow rates used were 0.5, 1.0, 2.0, and 3.0 ml/min with detection at 225 nm. The values of capacity, separation, and resolution factors ranged from 0.38 to 19.70, 1.08-2.33, and 1.0 and 4.50, respectively. The maximum and minimum resolutions were achieved for celiprolol and bufurolol, respectively. The chiral recognition mechanisms were also discussed. The values of validation parameters were calculated.