Synthesis, spectral analysis, DFT calculations, biological potential and molecular docking studies of indole appended pyrazolo-triazine.

A series of novel 5-(3,5-disubstituted-1H-indol-2-yl)-2,3-dimethyl-1-phenyl-2,6-dihydro-1H-pyrazolo[4,3-e][1,2,4]triazines (3a-l) were synthesized in single step from 3,5-disubstituted indole-2-carbohydrazide and 4-aminoantipyrine under acidic conditions with excellent yields. The various spectroscopic methods were used to prove the formation of all these products. The compounds 3a, 3b, 3e, 3f, 3i and 3j exhibited excellent antibacterial and antifungal activities with an MIC value of 3.125 µg/ml against the tested pathogens and anti-tuberculosis inhibitory potential against M. tuberculosis which is equivalent to standard drug. The antidiabetic activity of the compounds 3a and 3b showed the maximum potential as glucosidase inhibitors with IC50 = 47.21 µg/ml and IC50 = 48.36 µg/ml, respectively. The physicochemical characteristics like ADMET, drug-likeness and bioactivity scores for these molecules were also disclosed. To comprehend the electronic behavior of compound 3a, density functional theory estimations at the DFT/B3LYP level via 6-31G++ (d, p) have been carried out to replicate the structure and geometry. The first-order hyperpolarizability calculation was used to calculate the nonlinear visual feature of compound 3a. The charge transfer interface among the structure is elucidated by the estimated HOMO-LUMO analysis. Further, molecular docking studies were carried out for synthesized compounds with human maltase-glucoamylase (PDB: 2QMJ).

Evident stabilization of the clinical profile in HIV/AIDS as evaluated in an open label clinical trial using a polyherbal formulation.

BACKGROUND & OBJECTIVES: The complementary and alternative medicines (CAM) have not been systematically evaluated for the management of HIV/AIDS patients. In a prospective, single-site, open-label, non-randomized, controlled, pilot trial, we evaluated a polyherbal formulation (PHF) for its safety and efficacy in treating subjects with HIV-AIDS. METHODS: A total of 32 and 31 subjects were enrolled under the PHF and highly active antiretroviral treatment (HAART) arms, respectively, and followed up for a period of 24 months. Plasma viral RNA, CD4 cell count and blood chemistry were monitored at 3-month intervals. Following mid-term safety evaluation, 12 subjects from the PHF arm were shifted to HAART and were followed separately as PHF-to-HAART arm, for the rest of the period. RESULTS: The HAART arm was characterized by significant improvements in CD4 cell count (154.4 cells/µl/year, P<0.001) and reduction in plasma viral load within 3 to 6 months (-0.431+ 0.004 log 10 IU/month, P<0.001). In contrast, the PHF arm showed a profile of CD4 cell loss at remarkably slower kinetics (14.3 cells/µl/year, P=0.021) and insignificant reduction in the viral load. The PHF and HAART arms did not differ significantly in the occurrence of AIDS-related illnesses over the study period of 24 months. In the PHF-to-HAART arm, the rates of CD4 count and reduction in viral load were significant and comparable to that of the HAART group. In the PHF arm, at 1 month, a significant increase in CD4 cell count and a concomitant decrease in viral load were seen. INTERPRETATION & CONCLUSIONS: The PHF appears to have provided protection by delaying the kinetics of CD4 cell reduction. Given the several study limitations, drawing assertive inferences from the data is challenging. Future studies with a stringent study design are warranted to confirm these findings.