The zoonotic disease brucellosis, a chronic condition in humans affecting renal and cardiac systems and causing osteoarthritis, is caused by Brucella, a genus of Gram-negative, facultative, intracellular pathogens. The mode of transmission and the virulence of the pathogens are still enigmatic. Transcription regulatory elements, such as rho proteins, play an important role in the termination of transcription and/or the selection of genes in Brucella. Adverse effects of the transcription inhibitors play a key role in the non-successive transcription challenges faced by the pathogens. In the investigation presented here, we computationally predicted the transcription termination factor rho (TtFRho) inhibitors against Brucella melitensis 16M via a structure-based method. In view the unknown nature of its crystal structure, we constructed a robust three-dimensional homology model of TtFRho’s structure by comparative modeling with the crystal structure of the Escherichia coli TtFRho (Protein Data Bank ID: 1PVO) as a template in MODELLER (v 9.10). The modeled structure was optimized by applying a molecular dynamics simulation for 2 ns with the CHARMM (Chemistry at HARvard Macromolecular Mechanics) 27 force field in NAMD (NAnoscale Molecular Dynamics program; v 2.9) and then evaluated by calculating the stereochemical quality of the protein. The flexible docking for the interaction phenomenon of the template consists of ligand-related inhibitor molecules from the ZINC (ZINC Is Not Commercial) database using a structure-based virtual screening strategy against minimized TtFRho. Docking simulations revealed two inhibitors compounds – ZINC24934545 and ZINC72319544 – that showed high binding affinity among 2,829 drug analogs that bind with key active-site residues; these residues are considered for protein-ligand binding and unbinding pathways via steered molecular dynamics simulations. Arg215 in the model plays an important role in the stability of the protein-ligand complex via a hydrogen bonding interaction by aromatic-π contacts, and the ADMET (absorption, distribution, metabolism, and excretion) analysis of best leads indicate nontoxic in nature with good potential for drug development.

Aim:This study aims to isolate, characterize, and in silico evaluate of anticancer polyphenols from different parts of Syzygium alternifolium.Materials and Methods:The polyphenols were isolated by standard protocol and characterized using Fourier-transform infrared (FT-IR), High performance liquid chromatography - Photodiode array detector coupled with Electrospray ionization - mass spectrometry (MS/MS). The compounds were elucidated based on retention time and molecular ions (m/z) either by [M+H]+/[M-H]− with the comparison of standard phenols as well as ReSpect software tool. Furthermore, absorption, distribution, metabolism, and excretion (ADME)/toxicity properties of selected phenolic scaffolds were screened using OSIRIS and SwissADME programs, which incorporate toxicity risk assessments, pharmacokinetics, and rule of five principles. Molecular docking studies were carried out for selected toxicity filtered compounds against breast cancer estrogen receptor a (ERa) structure (protein data bank-ID: 1A52) through AutoDock scoring functions by PyRx virtual screening program.Results:The obtained results showed two intensive peaks in each polyphenol fraction analyzed with FT-IR, confirms O-H/C-O stretch of the phenolic functional group. A total of 40 compounds were obtained, which categorized as 9 different classes. Among them, flavonol group represents more number of polyphenols. In silico studies suggest seven compounds have the possibility to use as future nontoxic inhibitors. Molecular docking studies with ERa revealed the lead molecules unequivocally interact with Leu346, Glu353, Leu391, Arg394, Gly521, Leu525 residues, and Phe404 formed atomic π-stacking with dihydrochromen-4-one ring of ligands as like estrodial, which stabilizes the receptor structure and complicated to generate a single mutation for drug resistance.Conclusion:Overall, these results significantly proposed that isolated phenolics could be served as potential ER mitigators for breast cancer therapy.

The present study was to explore expectation and examination of therapeutic potential quercetin analogs as efficient anticancer agents against human epidermal growth factor receptor (EGFR), which is a consistent hallmark for moderating the non-small-cell lung carcinoma (NSCLC). Here, ligand-based virtual screening, pharmacophore approach and molecular docking were established as rational strategies for recognition of small analogs against the ligand binding domain of EGFR (PDB code: 1XKK). Adverse effects, toxicogenomics and pharmacokinetics reported that 10 candidates showed reliable consequences with less side effects and more efficient for target receptor. Protein-ligand interaction profiles revealed that the probable H-bonds, atomic-π contacts, salt bridges and van der Waals interactions sustain the complexity and stability of receptor structure; thus, they could complicate to generate single alteration acquired for drug resistance. In silico anticancer properties explain the lead scaffolds which are assumed to be flexible and experimentally proved chemicals. The overall consequences indicated that recognized leads could be utilized as reference skeletons for new inhibitors envisaging toward EGFR to ameliorate NSCLC and other malignant disorders.

Medicinal plants are unique in having the ability to produce diverse chemical compounds with remarkable biological activities. Investigations of medicinal plants resulted in the discovery of a large number of bioactive compounds with excellent therapeutic properties. Solanum surattense, a perennial wild growing medicinal herb, is widely used in the traditional medicine. Exhaustive literature availability reveals the presence of phytochemical compounds from different plant parts like roots, stem, leaves, fruits, and seeds reported to possess a wide range of pharmacological activities like hepatoprotective, cardioprotective, antiasthmatic and mosquito repellents properties. Intensive investigation on phytochemical constituents resulted in isolation of alkaloid and steroidal compounds solasonoine, solamargine, campesterol, and diosgenin. Evaluation of therapeutic activity of isolated compounds proved as potent ones with reference to the standard. Current literature on the pharmacological activity of S. surattense confirms the scientific validation of folklore claims and its traditional use to cure various ailments. Present review is undertaken to summarize all the available information on pharmacological activities, which provide a baseline support for further exploration of its unexplored therapeutic effects like immunomodulation, antipiles activity, antianaphylactic activity, and sexual behavior claimed by folklore.

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