Ranjan Khunt

Synthesis, antitubercular evaluation and 3D-QSAR study of N-phenyl-3-(4-fluorophenyl)-4-substituted pyrazole derivatives.

As a part of our ongoing research to develop novel antitubercular agents, a series of N-phenyl-3-(4-fluorophenyl)-4-substituted pyrazoles have been synthesized and tested for antimycobacterial activity in vitro against Mycobacterium tuberculosis H37Rv strain using the BACTEC 460 radiometric system. A 3D-QSAR study based on CoMFA and CoMSIA was performed on these pyrazole derivatives to correlate their chemical structures with the observed activity against M. tuberculosis. The CoMFA model provided a significant correlation of steric and electrostatic fields with the biological activity while the CoMSIA model could additionally shed light on the role of hydrogen bonding and hydrophobic features. The important features identified in the 3D-QSAR models have been used to propose new molecules whose activities are predicted higher than the existing systems. This study provides valuable directions to our ongoing endeavor of rationally designing more potent antitubercular agents.

Synthesis and 3D‐QSAR Analysis of 2‐Chloroquinoline Derivatives as H37RV MTB Inhibitors

Frequency of tuberculosis is progressively increasing worldwide. New emerging strains of bacilli that are emerging are resistant to the currently available drugs which make this issue more alarming. In this regard, a series of substituted quinolinyl chalcones, quinolinyl pyrimidines, and pyridines were synthesized and evaluated for their antitubercular activity in vitro against Mycobacterium tuberculosis H37RV. To establish the role of the 2‐chloroquinoline nucleus as a pharmacophoric group and study its influence on the antimycobacterial activity, a 3D‐QSAR study based on CoMFA and CoMSIA was undertaken on this set of 2‐chloroquinoline derivatives. Statistically significant models that are able to well correlate the antimycobacterial activity with the chemical structures of the 2‐chloroquinolines have been developed. The contour maps resulting from the best CoMFA and CoMSIA models were used to identify the structural features relevant to the biological activity in this series of analogs. Further analysis of these interaction‐field contour maps also showed a high level of internal consistency. The information obtained from the field 3‐D contour maps may be fruitfully utilized in the design of more potent 2‐chloroquinoline‐based analogs as potential antitubercular candidates.

Synthesis and biological evaluation of chalcones and acetyl pyrazoline derivatives comprising furan nucleus as an antitubercular agents

A series of 1-{5-[5-(m,p-dichlorophenyl)furan-2-yl]-3-aryl-4,5-dihydro-1H-pyrazol-1-yl} ethanone (3a–k) have been synthesized by the condensation of (2E)-3-[5-(m,p-dichlorophenyl)furan-2-yl]-1-arylprop-2-en-1-one (2a–k) with hydrazine hydrate in glacial acetic acid. The synthesized compounds have been characterized on the basis of elemental analyses and spectral studies. All the synthesized products have been screened for their antibacterial, antifungal, and antitubercular activity.

Dihedral angle study in Hesperidin using NMR Spectroscopy

Hesperidin is flavonoid molecule found in citrus fruits (Citrus reticulata), especially difficult to extract, classify and characterize. Present work is to study the unresolved relative configuration of Hesperidin through the dihedral angle, coupling constant and different NMR techniques. The Karplus equation and its modifications have been originated from the valence bond theory and associated with dihedral angle and coupling constant. The result data set of calculated dihedral angle can probe significant method to assign the virtual configuration of natural products and also resolved stereochemistry of Hesperidin at C‐2 position in. Copyright

Sonochemical synthesis, characterization, thermal and semiconducting behavior of nano-sized azidopentaamminecobalt(III) complexes containing anion, CrO42− or Cr2O72−

New nano-sized cobalt(III) coordination complexes, [Co(NH3)5N3]CrO4 (1N) and [Co(NH3)5N3]Cr2O7 (2N) were synthesized using an innovative sonochemical methodology based on reaction between [Co(NH3)5N3]Cl2 and potassium salt of CrO42- or Cr2O72- in aqueous medium. These complexes were also compared with their respective bulks which were synthesized under identical conditions in the absence of sonicaion. All the complexes were characterized by elemental analysis and spectroscopic techniques (UV-visible and IR). Morphology and particle size of nano-sized complexes was determined by SEM and Zeta-sizer respectively. TGA was used for comparative thermal stability and XRD to identify the phase difference between nano structures and bulk complexes. Furthermore, the electrical property was investigated and all complexes were found to be electrical semiconducting materials and 2N shows better result than others. The single crystals X-ray structure study of new [Co(NH3)5N3]Cr2O7 revealed the presence of discrete ions, [Co(NH3)5N3]2+ and Cr2O72-, crystallizes in monoclinic, space group Pc, with R=0.0636 in the solid state.

Method development and validation: quantitation of telmisartan bulk drug and its tablet formulation by 1H NMR spectroscopy: Quantitation of telmisartan by 1H NMR Spectroscopy

The quantitative NMR (qNMR) spectroscopy is nowadays a new tool for the determination of pharmaceutical potent biologically active molecules in bulk drug and its tablet formulation than the other analytical techniques. Herein, qNMR method was developed for an anti‐hypertensive drug, telmisartan in bulk drug and its tablet formulation. The precise method was developed by using malononitrile as an internal standard. The methylene signal of telmisartan appeared at δ = 5.46 ppm (singlet) relative to the signal of malononitrile at δ = 3.59 ppm (singlet) in CDCl3, as an NMR solvent. The development and validation of the method were carried out as per International Conference on Harmonization guidelines. The method was found to be linear (r2 = 0.9999) for 0.5 to 3.5 mg/ml in the drug concentration range. The relative standard deviation for accuracy and precession was not more than 2.0%. The sensitivity of the method was carried out by limit of detection and a limit of quantification, at 0.05 and 0.2 mg/ml, respectively, concentration. The robustness of the method was studied by changing parameters as well as different solvent manufacturer company. The result shows that method was accurately developed for quantification of telmisartan in pharmaceutical dosage form. The developed method by 1H NMR spectroscopy is comparatively easy and more precise with respect to the other analytical tools. Copyright

Importance of HMBC and NOE 2D NMR techniques for the confirmation of regioselectivity

In modern chemotherapy, versatile purine skeletons play central roles. The occurrences of the purine core in various natural sources have generated immense interest because of its remarkable therapeutic potentials. Among them, an extensive array of 6-amino-substituted derivatives of purine exhibits anticonvulsant, antiviral, antiinflammatory, antineoplastic, antiasthmatic, and antibacterial activities. Moreover, natural purines are found to be the core skeleton of nucleic acid, which are directly correlated with enzymes and proteins. Recently, the synthesis of 6-amino-substituted purine analogs was carried out by the amination of halogenated purines using organic solvents, such as n-butanol, acetonitrile, dioxane, DMF, and DMSO in the presence of versatile bases such as Et3N, N,N-dimethylcyclohexylamine, and diisopropylethylamine. Purine substitution is affected by its chemical properties, thus affecting the results in nuclear magnetic resonance (NMR) analysis like chemical shifts and coupling constants between atoms depending upon the electronic environment. As the chemical environment of both chlorine (C-2 and C-6) in purine base scaffold is identical, it was necessary to identify the regioselectivity of amination. This would be helpful for correct structure evaluation and to identify the interaction between nuclei. The present work includes the use of various techniques, for instance, H NMR, C NMR, nuclear Overhauser effect spectroscopy (NOESY), heteronuclear multiple-bond correlation spectroscopy (HMBC), and heteronuclear single-quantum coherence (HSQC), for the site selectivity of the reaction at C-2 or C-6 of the purine ring. Structural elucidation and relative configuration analysis of organic would be possible by using heteronuclear long-range coupling constants. The HMBC experiment is in principle the most suitable experiment to obtain information on heteronuclear longrange couplings because all long-range correlations are accessible, even those to unprotonated heteronuclear scaffolds. There are numerous advantages to these experiments over the traditional HETCOR experiment including increased sensitivity (0.5-mg sample is sufficient) and the ability to see a long-range interaction between C and H nuclei. HSQC is used to determine the particular relation of H with C nucleus (or other X nuclei). The advantage of inverse experiments over X detection experiment is that with inverse experiments, the nucleus with the highest magnetogyric ratio (usually H) is detected yielding the highest sensitivity. The combination of HSQC and HMBC constitutes the most powerful method available for tracing out the carbon skeleton of an organic compound.