Development of Azaindole-Based Frameworks as Potential Antiviral Agents and Their Future Perspectives.

The azaindole (AI) framework continues to play a significant role in the design of new antiviral agents. Modulating the position and isosteric replacement of the nitrogen atom of AI analogs notably influences the intrinsic physicochemical properties of lead compounds. The intra- and intermolecular interactions of AI derivatives with host receptors or viral proteins can also be fine tuned by carefully placing the nitrogen atom in the heterocyclic core. This wide-ranging perspective article focuses on AIs that have considerable utility in drug discovery programs against RNA viruses. The inhibition of influenza A, human immunodeficiency, respiratory syncytial, neurotropic alpha, dengue, ebola, and hepatitis C viruses by AI analogs is extensively reviewed to assess their plausible future potential in antiviral drug discovery. The binding interaction of AIs with the target protein is examined to derive a structural basis for designing new antiviral agents.

Vibrational spectra, NLO analysis, and HOMO-LUMO studies of 2-chloro-6-fluorobenzoic acid and 3,4-dichlorobenzoic acid by density functional method.

The FTIR and FT-Raman spectra of 2-chloro-6-fluorobenzoic acid and 3,4-dichlorobenzoic acid have been recorded in the region 4000-400 cm(-1) and 3500-50 cm(-1), respectively. Utilizing the observed FTIR and FT-Raman data, a complete vibrational assignment and analysis of fundamental modes of the compounds were carried out. The optimized molecular geometries, vibrational frequencies, thermodynamic properties and atomic charge of the compounds were calculated by using density functional theory (B3LYP) method with 6-311+G and 6-311++G basis sets. The difference between the observed and scaled wave number values of most of fundamentals is very small. Unambiguous vibration assignment of all the fundamentals is made up the total energy distribution (TED). The calculated HOMO and LUMO energies show that charge transfer occurs within the molecules. Besides, molecular electro static potential (MESP), Mulliken's charge analysis, first order hyper polarizability and several thermodynamic properties were performed by the DFT method.

Molecular structure, vibrational spectral assignments, HOMO-LUMO, MESP, Mulliken analysis and thermodynamic properties of 2,6-xylenol and 2,5-dimethyl cyclohexanol based on DFT calculation.

The FT-IR and FT-Raman spectra of 2,6-xylenol and 2,5-dimethyl cyclohexanol are recorded in the region 4000-400 cm(-1) and 3500-50 cm(-1) respectively. The spectral data obtained are assigned to different normal modes by using of comparison with the theoretical values obtained by applying density functional theory (DFT/B3LYP) method with 6-31+G and 6-31++G basis set. The total energy distribution contributions of vibrations modes are distinguished through scaling factors. The calculated HOMO and LUMO energies shows that the charge transfers occur within the molecules. The harmonic frequencies obtained from these two methods are compared. The Mulliken, molecular electrostatic potentials analysis are calculated theoretically.

Spectroscopic (FT-IR and FT-Raman) investigation, first order hyperpolarizability, NBO, HOMO-LUMO and MEP analysis of 6-nitrochromone by ab initio and density functional theory calculations.

The vibrational spectral analysis is carried out using FT-Raman and FT-IR spectroscopy in the range 3500-50 cm(-1) and 4000-400 cm(-1), respectively, for 6-nitrochromone (6NC). The molecular structure, fundamental vibrational frequencies and intensity of the vibrational bands are interpreted with the aid of structure optimization and normal coordinates force field calculation based on ab initio HF and DFT gradient calculations employing the HF/6-311++G(d,p) and B3LYP/6-311++G(d,p) basis set. Stability of the molecule has been analyzed using NBO analysis. The calculated HOMO and LUMO energies show that charge transfer occurs within the molecule. Thermodynamic properties like entropy, heat capacity, zero-point energy and Mulliken's charge analysis have been calculated for the 6NC. The complete assignments were performed on the basis of total energy distribution (TED) of the vibrational modes with scaled quantum mechanical (SQM) method. The MEP map shows the negative potential sites are on oxygen atoms as well as the positive potential sites are around the hydrogen atoms.

Vibrational spectral investigation, NBO, first hyperpolarizability and UV-Vis spectral analysis of 3,5-dichlorobenzonitrile and m-bromobenzonitrile by ab initio and density functional theory methods.

The FT-IR and FT-Raman spectra of 3,5-dichlorobenzonitrile and m-bromobenzonitrile have been recorded in the region 4000-400 cm(-1) and 3500-50 cm(-1), respectively. The optimized geometry, wave numbers and intensity of vibrational bonds of title molecules are obtained by ab initio and DFT level of theory with complete relaxation in the potential energy surface using 6-311++G(d, p) basis set. A complete vibrational assignments aided by the theoretical harmonic frequency, analysis have been proposed. The harmonic vibrational frequencies calculated have been compared with experimental FT-IR and FT-Raman spectra. The observed and calculated frequencies are found to be in good agreement. Stability of the molecule arising from hyperconjugative interactions, charge delocalization have been analyzed using natural bond orbital (NBO) analysis. The UV-Vis spectral analysis of the molecules has also been done which confirms the charge transfer of the molecules. Furthermore, the first hyperpolarizability and total dipole moment of the molecules have been calculated.

Vibrational analysis of 4-amino pyrazolo (3,4-d) pyrimidine A joint FTIR, Laser Raman and scaled quantum mechanical studies.

The FTIR and Laser Raman spectra of 4-amino pyrazolo (3,4-d) pyrimidine have been measured in the regions 4000-400 cm(-1) and 3500-100 cm(-1), respectively. Utilizing the observed FTIR and Laser Raman data, a complete vibrational assignment and analysis of the fundamental modes of the title compound were carried out. The vibrational frequency which were determined experimentally are compared with those theoretically from force field calculation based on ab initio HF/6-311+G**(d,p) and standard B3LYP/6-311+G**(d,p) methods and basis set combinations for optimized geometries. The observed FTIR and Laser Raman vibrational frequencies were analysed and compared with the theoretically predicted vibrational frequencies. The assignments of bands to various normal modes of the molecules were also carried out. A detailed interpretation of the infrared and Raman spectra of 4-amino pyrazolo (3,4-d) pyrimidine [4AP(3,4-D)P] is also reported based on total energy distribution (TED). The calculated HOMO and LUMO energies shows that charge transfer occur within the molecule. The theoretical FT-IR and FT-Raman spectra for the title molecule have also been constructed.

Novel 8-(furan-2-yl)-3-benzyl thiazolo [5,4-e][1,2,4] triazolo [1,5-c] pyrimidine-2(3H)-thione as selective adenosine A(2A) receptor antagonist.

Adenosine A(2A) receptor (A(2A)R) antagonists have emerged as potential drug candidates to alleviate progression and symptoms of Parkinson's disease (PD), and reduce the dopaminergic side effects. The synthesis of novel compound 8-(furan-2-yl)-3-benzyl thiazolo [5,4-e][1,2,4] triazolo [1,5-c] pyrimidine-2-(3H)-thione (BTTP) was carried out to evaluate the potential of BTTP as A(2A)R antagonist using SCH58261, a standard A(2A)R antagonist. The strong interaction of BTTP with A(2A)R (ΔG=-12.46kcal/mol and K(i)=0.6nM) in silico analysis was confirmed by radioligand receptor binding studies showing high affinity (K(i)=0.004nM) and selectivity with A(2A)R (A(2A)/A(1)=1155-fold). The effect of CGS21680 (selective A(2A)R agonist) induced cAMP concentration (0.1pmol/ml) in HEK293 cells was antagonized with BTTP (0.065pmol/ml) and SCH58261 (0.075pmol/ml). Furthermore, BTTP pre-treated (5, 10 and 20mg/kg) haloperidol-induced mice demonstrated significant attenuation in catalepsy and akinesia. BTTP induced elevation in the striatal dopamine concentration (2.90µM/mg of tissue) was comparable to SCH58261 (2.92µM/mg of tissue) at the dose of 10mg/kg. The results firmly articulate that BTTP possesses potential A(2A)R antagonist activity and can be further explored for the treatment of PD.

Novel 8-(furan-2-yl)-3-substituted thiazolo [5,4-e][1,2,4] triazolo[1,5-c] pyrimidine-2(3H)-thione derivatives as potential adenosine A(2A) receptor antagonists.

Novel thiazolotriazolopyrimidine derivatives (23-33) designed as potential adenosine A(2A) receptor (A(2A)R) antagonists were synthesized. Molecular docking studies revealed that all compounds (23-33) exhibited strong interaction with A(2A)R. The strong interaction of the compounds (23-33) with A(2A)R in silico was confirmed by their high binding affinity with human A(2A)R stably expressed in HEK293 cells using radioligand-binding assay. The compounds 24-26 demonstrated substantial binding affinity and selectivity for A(2A)R as compared to SCH58261, a standard A(2A)R antagonist. Decrease in A(2A)R-coupled release of endogenous cAMP in treated HEK293 cells demonstrated in vitro A(2A)R antagonist potential of the compounds 24-26. Attenuation in haloperidol-induced motor impairments (catalepsy and akinesia) in Swiss albino male mice pre-treated with compounds 24-26 further supports their role in the alleviation of PD symptoms.

Effects of Vitamin C and E on PCB (Aroclor 1254) induced oxidative stress, androgen binding protein and lactate in rat Sertoli cells.

The effect of Aroclor 1254 and the ameliorative effect of Vitamin C and E on Sertoli cell function were studied in adult male rats. The rats were administered Aroclor 1254 at a dose of 2 mg/kg bw/day intraperitoneally for 30 days. One group of rats received Vitamin C (100 mg/kg bw/day) while the other group received Vitamin E (50 mg/kg bw/day) orally simultaneously with Aroclor 1254 for 30 days. Necropsy was performed at 24 h after the last injection. Sertoli cells were isolated for the estimation of enzymatic antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GST), and gamma-glutamyl transpeptidase (gamma-GT). Lipid peroxidation (LPO), hydrogen peroxide and hydroxyl radical were estimated. Sertoli cellular androgen binding protein (ABP) and lactate were also quantified. Whereas body weight, testis weight, relative weight of testis, ABP, lactate and specific activities of SOD, CAT, GPx, GR, GST, gamma-GT were all decreased, the levels of hydrogen peroxide, hydroxyl radical and LPO were significantly increased in the Sertoli cells of Aroclor 1254 treated rats. Simultaneous administration of Vitamin C or E restored these parameters to a normal range. Thus, the present study suggests that Aroclor 1254 exposure induces oxidative stress in rat Sertoli cells and furthermore that simultaneous administration of Vitamin C or E ameliorated these effects.