Mazahar Farooqui

Chemistry and Biology of Indoles and Indazoles: A Mini-Review

The present review article is related with the method of preparation, importance and medicinal application of indole and indazoles. The studies of heterocycles is an evergreen field in the branch of organic chemistry and always attract the attention of chemists working not only in the area of natural products but also in the synthetic chemistry. Moreover many useful drugs have emerged from the successful investigation carried out in this branch. The derivatives of indoles and indazoles exhibits antibacterial, anticancer, antionidants, anti-inflammatory, antidiabetic, antiviral, atniproliferative, antituberculosis, antispermetogenic activity, antipsychotic drugs etc.

Synthesis of new α aminophosphonate system bearing Indazole moiety and their biological activity.

We are reporting herein for the first time the synthesis of α-aminophosphonates containing Indazole moiety in two steps. In the first step, imines of substituted N-benzylidene-1-methyl-1H-indazole-3-carbohydrazide are synthesized and in the next step it has converted to α-aminophosphonates using chlorotrimethylsilane (TMSCl) and triethyl phosphite. Some of the synthesized derivatives are evaluated for antibacterial activity against different bacterial strains.

Development and validation of a stability indicating RP-HPLC method for the simultaneous determination of related substances of albuterol sulfate and ipratropium bromide in nasal solution.

A simple, sensitive and specific RP-HPLC method was developed for the quantification of related impurities of albuterol sulfate (AS) and ipratropium bromide (IB) in liquid pharmaceutical dosage form. The chromatographic separation employs gradient elution using an inertsil C8-3, 250mmx4.6mm, 5mum columns. Mobile phase consisting of solvent A (solution containing 2.5g of potassium dihydrogen phosphate and 2.87g of heptane-1-sulfonic acid sodium salt per liter of water, adjusted to pH 4 with orthophosphoric acid) and solvent B (acetonitrile) delivered at a flow rate of 1.0mlmin(-1). The analytes were detected and quantified at 210nm using photodiode array (PDA) detector. The method was validated as per ICH guidelines, demonstrating to be accurate and precise (repeatability and intermediate precision level) within the corresponding linear range of known impurities of AS and IB. The specificity of the method was investigated under different stress conditions including hydrolytic, oxidative, photolytic and thermal as recommended by ICH guidelines. Relevant degradation was found to take place under hydrolytic and oxidative conditions. Robustness against small modification in pH, column oven temperature, flow rate and percentage of the mobile phase composition was ascertained. Lower limit of quantification and detection were also determined. The peak purity indices (purity angle<purity threshold) obtained with the aid of PDA detection and satisfactory resolution between related impurities established the specificity of the determination. All these results provide the stability indicating capability of the method.

[1, 2, 4]-Oxadiazoles: Synthesis and Biological Applications

In the present article synthesis and medicinal applications of [1, 2, 4] oxadiazoles are reviewed. The oxadiazoles have a wide range of applications such as Antitussive, Anti-inflammatory, Anaesthetic, Vasodilator, anthelmintic, antiallergic, antiplatelet effects in vitro, antithrombotic properties in vivo, etc. Many researchers have synthesized novel heterocyclic compounds containing oxadiazoles with the concept of bioisosterism.

VALIDATED RP-LC-MS/MS METHOD FOR THE SIMULTANEOUS DETERMINATION OF ALLOPURINOL AND ITS MAJOR METABOLITE, OXYPURINOL, IN HUMAN PLASMA

A rapid and highly sensitive LC-MS/MS method was developed and validated for the determination of allopurinol (AP) and its major metabolite, oxypurinol (OP) in human plasma using lamivudine as an internal standard (IS). The analytes were extracted from human plasma by protein precipitation using acetonitrile. The chromatographic separation was employed on “waters symmetry shield RP8, 150 mm × 3.9 mm, 5 μm” columns using a mixture of 0.01% formic acid in water and acetonitrile in the ratio of 95:05 (v/v) as the mobile phase. Mass spectrometer in the selected reaction-monitoring mode with negative electro spray was used for the detection and quantification of the analyte. Recovery study was performed showing the accuracy at upper and lower limits of quantification. The stability study was also carried out. The described method was found to be linear over a range of 0.01–10 μg mL−1 with a lower limit of quantification of 0.01 μg mL−1 for both AP and OP. The coefficient of variation for the assay precision was found <6.94, and the accuracy was found >96.03. The extraction recoveries for AP and OP were found to be in between 70 and 80%, the accuracy was found to be in between 95 and 106% in human plasma. The dilution integrity test, hemolysis and anticoagulant effect, and matrix effect studies were reported.

Antileishmanial evaluation of clubbed bis(indolyl)-pyridine derivatives: One-pot synthesis, in vitro biological evaluations and in silico ADME prediction

A new series of bis(indolyl)-pyridine derivatives 6(a-m) were synthesized by Chichibabin reaction process and evaluated for antileishmanial and antibacterial activities to establish structure-activity relationship. The synthesis was carried out through one-pot multicomponent reaction of 3-acetylindole, aromatic aldehydes, and ammonium acetate in the presence of camphor-10-sulfonic acid as a catalyst. The compounds 6d (IC50=102.47μM) and 6f (IC50=99.49μM) had shown promising antileishmanial against L. donovani promastigotes when compared with standard sodium stibogluconate (IC50=490.00μM). All the synthesized compounds (MIC range=41.35-228.69μg/mL) had shown potent antibacterial activity than standard ampicillin (MIC range=100.00-250.00μg/mL) against all the tested bacterial strains. In silico ADME and metabolic site prediction studies were also held out to set an effective lead candidate for the future antileishmanial and antibacterial drug discovery initiatives.

Solvent-free, scalable and expeditious synthesis of benzanilides under microwave irradiation using clay doped with palladium nanoparticles as a recyclable and efficient catalyst

Benzanilide synthesis through amide bond formation was effectively carried out by palladium-doped clay catalyst using microwave irradiation under solvent-free conditions. Products were obtained with excellent yield in very short reaction time and only a small amount of the catalyst was used. The catalyst could be separated easily and recycled several times with insignificant loss in catalytic activity. No column purification was required and the products were purified by the crystallization method. The heterogeneous character of the catalyst in a ligand-free, solvent-free and base-free system supports for a practical and environmentally benign process.

Efficient synthesis of tertiary amine by direct N-alkylation of secondary amine with carboxylic acid using Ni (0) encat catalyst

ABSTRACT In this article, direct N-alkylation of secondary amines with carboxylic acid is described. Readily available diversified carboxylic acid has been explored on variant secondary amines using encapsulated Nickel as catalyst and inexpensive sodium borohydride as the hydride source. High yields, mild reaction conditions, tolerance to sensitive functional group and facile operational procedure are the significance of the present methodology. GRAPHICAL ABSTRACT

Supercritical carbon dioxide extraction and gas chromatography–mass spectrometry analysis of Gymnema sylvestre R.Br. roots

ABSTRACT Supercritical fluid extraction (SFE) achieves a wide range of applications since the past decade as a sustainable green technology. The present study investigates the process for producing high yield by supercritical carbon dioxide (Sc-CO2) extraction form Gymnema sylvestre R.Br. roots. The effect of temperature and pressure on the percentage of accumulative yield is demonstrated. It is found that the highest yield is obtained at the temperature of 60°C and the pressure of 10 MPa. A proper review showed that there is a lack in the study of Sc-CO2 extraction of this plant especially for optimization of SFE process which makes this study useful and valuable. For more benefit, the extract which achieves highest percentage is subjected to gas chromatography–mass spectrometry to study its chemical composition and detect the active principle compounds which present with high concentration and expected to be responsible of the pharmaceutical properties of the extract. GRAPHICAL ABSTRACT

Screening of Antioxidant Property and Phytochemical Constituents of Ethereal Extract of Vitex nigundo Linn Leaves

Vitex negundo belongs to the family Verbenaceae. Literature survey of the plant reveal that the vitex negundo possess antimicrobial, anti-inflammatory, analgesic, antibacterial, antifungal, anti-insects activities. In the present study the phytochemical compounds present in the ether extract of vitex negundo linn leaves extract analyzed and the free radical scavenging capacity of the extract. The experimental data showed that the ether extract of vitex negundo linn contain alkaloids, carbohydrate, glycosides, amino acids, proteins, tannins and phenolic compounds. The free radical scavenging capacity of the sample was measured by DPPH (2, 2-diphenyl-1-picrylhydrazyl) method. The IC50 value of the ascorbic acid which is used as the standard is 14.97 while for sample is 46.84. the ether extract of vitex negundo leaves shows good antioxidant property.