Tackling breast cancer with gold nanoparticles: twinning synthesis and particle engineering with efficacy.

The World Health Organization identifies breast cancer as the most prevalent cancer despite predominantly affecting women. Surgery, hormonal therapy, chemotherapy, and radiation therapy are the current treatment modalities. Site-directed nanotherapeutics, engineered with multidimensional functionality are now the frontrunners in breast cancer diagnosis and treatment. Gold nanoparticles with their unique colloidal, optical, quantum, magnetic, mechanical, and electrical properties have become the most valuable weapon in this arsenal. Their advantages include facile modulation of shape and size, a high degree of reproducibility and stability, biocompatibility, and ease of particle engineering to induce multifunctionality. Additionally, the surface plasmon oscillation and high atomic number of gold provide distinct advantages for tailor-made diagnosis, therapy or theranostic applications in breast cancer such as photothermal therapy, radiotherapy, molecular labeling, imaging, and sensing. Although pre-clinical and clinical data are promising for nano-dimensional gold, their clinical translation is hampered by toxicity signs in major organs like the liver, kidneys and spleen. This has instigated global scientific brainstorming to explore feasible particle synthesis and engineering techniques to simultaneously improve the efficacy and versatility and widen the safety window of gold nanoparticles. The present work marks the first study on gold nanoparticle design and maneuvering techniques, elucidating their impact on the pharmacodynamics character and providing a clear-cut scientific roadmap for their fast-track entry into clinical practice.

Synthesis, spectroscopic analysis, and computational-based investigations on 'azo-coumarin-Co(II)-galangin' hybrids exhibit multipotential activities.

The present study synthesized a series of cobalt (II) metal ion frame hybrid candidates (6a-6f) bearing phyto-flavonol galangin with substituted aryl diazenyl coumarins, and further structural confirmation was validated by various spectral techniques, including NMR, ATR-FTIR, UV-vis, HPLC, XRD, etc. Therapeutic potency was investigated via PASS (prediction of activity spectra for substances), molecular docking, molecular dynamics simulation, prediction of toxicity, pharmacokinetics, and drug-likeness scores, along with the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), with their energy gaps (ΔEH-L) to locate the most potential therapeutic candidates. The PASS prediction (Pa > Pi score) showed that proposed metal complexes have kinase inhibitors, antioxidative, and antischistosomal activities with potential molecular docking scores (> -7 kcal/mol) against selected targeted enzymes. Further, the MD-simulation (RMSD, RMSF, Rg, and H-bonds) of the most potential docking complex, 'HER2-6d', showed a minimum deviation similar to the standard drug (lapatinib) at 100 ns, indicating that 6d could be a potential noncovalent anticancer inhibitor. In addition, metal complexes possess a non-toxic and ideal drug-ability profiles, and positive electron space in an excited state increases the binding affinity towards target enzymes. Among all six ligands, 6c and 6d were the two most multipotent therapeutic agents from the above analyses. In summary, this could be a feasible approach towards the utilization of phytochemicals in mainstream therapeutic applications, where bioinformatics tools help to select a lead drug candidate at an early stage and guide for higher experimental success by proceeding with potential candidates.Communicated by Ramaswamy H. Sarma.

Isolation, characterization, and multimodal evaluation of novel glycolipid biosurfactant derived from Bacillus species: A promising Staphylococcus aureus tyrosyl-tRNA synthetase inhibitor through molecular docking and MD simulations.

Glycolipid-based biosurfactants (BSs), known for their intriguing and diverse properties, represent a largely uncharted territory in the realm of potential biomedical applications. This field holds great promise yet remains largely unexplored. This investigation provides new insights into the isolation, characterization, and comprehensive biomedical assessment of a novel glycolipid biosurfactant derived from Bacillus species, meeting the growing demand for understanding its multifaceted impact on various biomedical issues. Within this framework, two glycolipids, BG2A and BG2B, emerged as the most proficient strains in biosurfactant (BS) production. The biosurfactants (BSs) ascertained as glycolipids via thin layer chromatography (TLC) exhibited antimicrobial activity against S. aureus and E. coli. Both isolates exhibited anticancer effects against cervical carcinoma cells and demonstrated significant anti-biofilm activity against V. cholerae. Moreover, molecular docking and molecular dynamics (MD) simulations were employed to explore their antimicrobial resistance properties against Tyrosyl-tRNA synthetase (TyrRS) of Staphylococcus aureus, a well-annotated molecular target. Characterization and interpretation using Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (1H and 13C NMR) confirmed that the BSs produced by each strain were glycolipids. These findings suggest that the isolated BSs can serve as effective agents with antibiofilm, antimicrobial, antioxidant, and anticancer properties, in addition to their considerable antibacterial resistance attributes.

Nanosynthesis, phycochemical constituents, and pharmacological properties of cyanobacterium Oscillatoria sp.

The Oscillatoria sp., a blue-green alga or cyanobacterium, consists of about 305 species distributed globally. Cyanobacteria are prokaryotes possessing several secondary metabolites that have industrial and biomedical applications. Particularly, the published reviews on Oscillatoria sp. have not recorded any pharmacology, or possible details, while the detailed chemical structures of the alga are reported in the literature. Hence, this study considers pertinent pharmacological activities of the plethora of bioactive components of Oscillatoria sp. Furthermore, the metallic nanoparticles produced with Oscillatoria sp. were documented for plausible antibacterial, antifungal, antioxidant, anticancer, and cytotoxic effects against several cultured human cell lines. The antimicrobial activities of solvent extracts of Oscillatoria sp. and the biotic activities of its derivatives, pyridine, acridine, fatty acids, and triazine were structurally described in detail. To understand the connotations with research gaps and provide some pertinent prospective suggestions for further research on cyanobacteria as potent sources of pharmaceutical utilities, attempts were documented. The compounds of Oscillatoria sp. are a potent source of secondary metabolites that inhibit the cancer cell lines, in vitro. It could be expected that by holistic exploitation, the natural Oscillatoria products, as the source of chemical varieties and comparatively more potent inhibitors, would be explored against pharmacological activities with the integument of SARs.

In-vitro anticancer evaluation of newly designed and characterized tri/tetra-substituted imidazole congeners- maternal embryonic leucine zipper kinase inhibitors: Molecular docking and MD simulation approaches.

Our cascading attempt to develop new potent molecules now involves designing a series of imidazole derivatives and synthesizing two sets of 2,4,5- tri-substituted (4a-4d) and 1,2,4,5-tetra-substituted (6a-6d) imidazole by the principle of Debus-Radziszewski multicomponent synthesis reaction. The structures of the obtained compounds were confirmed by 1H/13C NMR, FT-IR, elemental analysis, purity and the retention time was analyzed by HPLC. Based upon the binding affinity in the molecular docking studies, we have synthesized different imidazole derivatives from which compound 6c have been found to show more anti-proliferative activity by inducing apoptosis at a higher rate than the other compounds corroborating the in-silico prediction. The structure and crystallinity of compound 4d have been confirmed by single XRD analysis. The synthesized molecules were screened for their in vitro anti-cancer properties in triple negative breast cancer cell line (MDA-MB-231), pancreatic cancer cell lines (MIA PaCa-2) and oral squamous cell carcinoma cell line (H357) and results indicated that all the compounds inhibited the cell proliferation in a concentration-dependent manner at different time points. The compounds 4b and 6d were found to be effective against the S. aureus bacterial strain whereas only compound 4d fairly inhibited the fungal strain of T. rubrum with a MIC 12.5 µg/mL. Molecular docking study reveals good interaction of the synthesized compounds with known target MELK involved in oncogenesis having high binding profiles. The lead compound 6c was further analyzed by the detailed molecular dynamics study to establish the stability of the ligand-enzyme complex.

Role of phytocompounds as the potential anti-viral agent: an overview.

Viral diseases are the most notorious infective agent(s) causing morbidity and mortality in every nook and corner for ages; viruses are active in host cells, and specific anti-virus medicines' developments remain uncanny. In this century of the biological era, human viruses act predominantly as versatile spreaders. The infection of the present COVID-19 virus is up in the air; blithely, the integument of medicinal chemistry approaches, particularly bioactive derived phytocompounds could be helpful to control those human viruses, recognized in the last 100 years. Indeed, natural products are being used for various therapeutic purposes. The major bioactive phytocompounds are chemically containing coumarin, thiosulfonate, steroid, polysaccharide, tannin, lignin, proanthocyanidin, terpene, quinone, saponin, flavonoid, alkaloid, and polyphenol, that are documented for inhibitory action against several viral infections. Mostly, about 20-30% of plants from tropical or temperate regions are known to have some antiviral activity. This comprehensive analysis of bioactive-derived phytocompounds would represent a significant impact and might be helpful for antiviral research and the current state of viral treatments.

Molecular dynamics simulation, synthesis and topoisomerase inhibitory actions of vanillin derivatives: a systematic computational structural integument.

A series of 4-hydroxy-3-methoxy benzaldehyde (vanillin) derivatives (3a-3r) was designed for the principle of Schiff base condensation with several individual sulfanilamide analogues. The inhibitory potencies of the designed compounds were evaluated through molecular docking simulation studies against the targets, breast cancer-topo isomerase-IIα and estrogen receptor-α; and the top scoring poses with higher binding energy were selected to assess the mode of binding and stability of each complex through molecular dynamics simulations. Compounds that remained stable in the active sites of the both target receptors through a number of strong H-bonds and hydrophobic contacts were selected. Based on the computational results, these selected compounds, 3b, 3e and 3f were synthesized and were followed up for structural elucidation attempts, by FT/ATR, 1H NMR and 13C NMR. From the experimental in vitro studies on 3b, 3e and 3f, the following remarkable activities against breast cancer cell line were done; IC50 values of 3b, 3e and 3f were noted, 6.7, 4.3 and 11 ng/mL, respectively. These newly synthesized compounds may be used as novel inhibitors of nuclear receptors with potential therapeutic applications in control of cancer.Communicated by Ramaswamy H. Sarma.

The recent development of thymol derivative as a promising pharmacological scaffold.

Thymol (a phenol ring bearing active phytoconstituent) is a privileged scaffold, which is diversified in natural sources. This scaffold acts as an obligatory template for scheming and arriving at designing some newer drug-molecules with potential biological activities. In the pharmacological perspective, the promising active sites of the scaffold are the positions C-1, C-4, and C-6 of thymol that would be accountable for developing potent drug candidates. This review aims to explore the various synthetic routes and the structural-activity relationship of thymol scaffold with suitable active pharmacophore sites.

Molecules with versatile biological activities bearing antipyrinyl nucleus as pharmacophore.

Antipyrine (1,2-dihydro-1,5-dimethyl-2-phenylpyrazole-3-one) in a structural frame consists of a five membered lactam pyrazolone heterocyclic ring as a pharmacophore moiety. It is evident from literature that the molecules having nitrogen bearing heterocyclic nuclei clearly exhibit several biological actions. Commercially available pyrazolone derivatives as drugs, analgin and metamizol are an established chemical class of analgesics. Recent trends of synthetic routes and several biological actions of antipyrine analogues are considered in this review. Indeed, the synthesized derivatives possess antipyrine moiety having versatile biological properties, antimicrobial, antitubercular, anthelmintic, antioxidant, analgesic, anti-inflammatory, cytotoxic and antiviral activities.

Norharmane as a potential chemical entity for development of anticancer drugs.

Cancer is a leading cause of death generally, and to overcome this problem the introduction of a new drug developing is a continuous endeavour. An alkaloid, norharmane and its derivatives, which have anticancer activities, widely distributed in several living and synthetic chemical sources. Herewith, the suggested mechanisms of organic reactions and synthetic approaches of norharmane available so far were considered. Active sites of norharmane nucleus positions, C-1, C-3, and N-9, were used for developing new molecules and based on structure activity relationship (SAR), those have been seen with anticancer activities. This review summarizes on chemistry of synthetic strategies of norharmane derivatives, which may provide a framework to design a novel anticancer drug, in future.