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Background: A series of bis(indolyl)methanes (3a-3o) have been synthesized using a greener and new approach using the reaction of different substituted aldehydes and indole in the presence of an easily available and biodegradable base such as piperidine in acetic acid at room temperature and characterized with UV (Ultraviolet-visible spectroscopy), Gas Chromatography-Mass Spectrometry (GCMS), Proton Nuclear Magnetic Resonance (H-NMR), and Fourier Transform Infrared Spectroscopy (FTIR). Methods: All 15 newly synthesized compounds (3a-3o) were subjected to in-vitro anti-microbial activity determination and compared with the known standard drug ciprofloxacin (1-2 μg/mL). Our in-silico analysis on the target protein, pdb id: 1d7u suggested that these analogues would be highly active against bacterial targets and thus, would act as good antimicrobial agents. Results: All 15 newly synthesized compounds (3a-3o) displayed potent activity on various experimental microbial strains (1.0-1.4 μg/mL). Compound, 3k was obtained as the best docked compound against common bacterial target enzyme, (pdb id:1d7u). The standard, Ciprofloxacin, retained the docking score of -111.3 Kcal/mol with similar binding amino acid residues (LYS272 (Pi-cation); ALA A:245 (Pisigma); TRP A:138 (Pi-Pi); ALA A:112; and MET A:141 (Pi-alkyl)) as of inbound. Conclusion : We believe that our current study would shed more light on the development of potent bis(indolyl)methanes as antimicrobial agents.

Background: Tuberculosis (TB) continues to be the most threatening cause of death in recent years. There is urgent need of search more potent, less toxic antitubercular agents. Methods: A set of five new 1,3,4-oxadiazolyl-imidazo-1,2-pyridine derivatives (4a-4e) was synthesized and screened invitro for their antibacterial activity against Mycobacterium tuberculosis (H37 RV strain) ATCC No-27294. Results: Compound 4b displayed potent antitubercular activity at MIC 6.25 µg/mL. In-silico molecular docking studies were performed for evaluation of the binding patterns of compounds 4a-4e in the binding site of proteins like, Pantothenate synthatase and enoyl acyl reductase inhibitor. The outcomes of the in- vitro antitubercular studies were in well agreement with the molecular docking studies. These newly synthesized compounds were found to have good ADMET profile. We also explored possible anticancer activity using in-silico methods. Conclusion: These results shows that readily synthesized 1,3,4-oxadiazolyl-imidazo-1,2-pyridine derivatives (4a-4e) are attracting new class of potent anti-TB targets as well as possible anticancer activity that worth additional opportunities for improvements.

Background: A simple and sensitive quantitation analytical technique by liquid chromatography–tandem mass spectrometry (LC-MS/MS) is essential for fedratinib in biological media with kinetic study in healthy rabbits. Objective: The main objectives of the present research work are to LC-MS/MS method development and validate procedure for the quantitation of fedratinib and its application to kinetic study in rabbits. Methods: Separation of processed samples were employed on zorbax SB C18 column (50mm×4.6 mm) 3.5µm with a movable phase of methanol, acetonitrile and 0.1% formic acid in the ratio of 30:60:10. The movable phase was monitored through column at 0.8 ml/min flow rate. The drug and ibrutinib internal standard (IS) were evaluated by monitoring the transitions of m/z -525.260/57.07 and 441.2/55.01 for fedratinib and IS respectively in multiple reaction monitoring mode. Results: The linear equation and coefficient of correlation (R2) results were y =0.00348x+0.00245 and 0.9984, respectively. Intra and inter-day precision RSD findings of the developed technique were found in the range of 2.4 - 5.3% for the quality control (QC)-samples (252.56, 1804.0 and 2706 ng/ml). The proposed method was subjected to pharmacokinetic study in healthy rabbits and the kinetic study, fedratinib showed mean AUClast 13190±18.1 hr*ng/ml and Cmax was found to be 3550±4.31 ng/ml in healthy rabbits. Conclusion: The validated method can be applicable for the pharmacokinetic and toxicokinetic studies in the clinical and forensic analysis of fedratinib in different kinds of biological matrices successfully.

Background: The bis(indolyl)methanes (BIMs) scaffold is reported for wide varieties of pharmacological profiles, including antibacterial, anti-proliferative, anticancer, cytotoxic, insecticidal, analgesic, antioxidant, and anti-inflammatory agents. Materials and Methods: A series of bis(indolyl)methanes have been synthesized by a greener and newer approach using the reaction of different substituted aldehydes and indole in the presence of an easily available and biodegradable base such as piperidine in acetic acid at room temperature and characterized with ultraviolet–visible spectrophotometry (UV–Vis or UV/Vis), Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), etc. The antibacterial and antifungal activities were also carried out against Staphylococcus aureus (RCMB 000106) and Bacillis subtilis (RCMB 000107), as two Gram-positive bacterial strains, and Salmonella typhi and Escherichia coli (RCMB 000103), as two Gram-negative bacterial strains. Fungal species such as Candida Albicans, Penicillium chrysogenum, Aspergillus niger were also used for in vitro antifungal evaluation. All our newly synthesized 14 compounds (4a-4n) were subjected for anti-inflammatory activity in vitro and compared with the known standard drug aceclofenac. Results: Our newly synthesized compounds showed good to moderate antibacterial agents, in silico ADMET, and anti-inflammatory profiles. Conclusion: We hope that our current study would aid future developments of bis(indolyl)methanes as antibacterial and anti-inflammatory agents.

Background:: Phyllanthus fraternus Webster Linn (family, Euphorbiaceae) is used as a traditional medication for the treatment of various disorders and has therapeutic implications. Objective:: This study intends to investigate the anxiolytic potential of Phyllanthus fraternus standardized extract and prediction of the probable role of its marker phytoconstituents. Methods:: We tested the standardized hydro-ethanolic extract of Phyllanthus fraternus (whole plant) for the Elevated plus-maze model (EPM) and Light & Dark Exploration test as classical models for anxiety. Phyto-chemical HPTLC fingerprint analysis was performed for the detection of two classes of compounds lignans and tannins. HPTLC analysis of the standardized extract was performed using phyllanthin hypophyllanthin and corilagin as marker compounds. Additionally, GABA receptor antagonism was studied in other sets of experiments to assess the involvement of this receptor in the anxiolytic- like effects produced by Phyllanthus fraternus. Results:: The lower doses of the lignan and tannin-rich extract of the Phyllanthus fraternus possess significant anxiolytic-like activity compared to the standard diazepam. Additionally, the results of the present study suggested that high doses (400mg/kg) of Phyllanthus fraternus have exerted some sedative- like effects. Phytochemical screening and HPTLC fingerprint analysis indicate the presence of lignans and tannins, whereas HPLC analysis of the standardized extract revealed the presence of marker lignan (Hypophyllanthin) and Tannin (Corilagin). The anxiolytic-like effect of Phyllanthus fraternus observed in the mice models were blocked by Flumazenil indicating the involvement of GABAA receptors in the modulation of this effect. Our molecular docking studies also supported probable anxiolytic and sedative effects. Conclusion:: To summarize, results support the use of Phyllanthus fraternus in the anxiety-like symptoms/ disease condition and suggest its anxiolytic-like effect governed by the GABA-A receptors.