Search

Neglected tropical diseases (NTDs) as termed by WHO include twenty different infectious diseases that are caused by bacteria, viruses, and parasites. Among these NTDs, Chagas disease and leishmaniasis are reported to cause high mortality in humans and are further associated with the limitations of existing drugs like severe toxicity and drug resistance. The above hitches have rendered researchers to focus on developing alternatives and novel therapeutics for the treatment of these diseases. In the past decade, several target-based drugs have emerged, which focus on specific biochemical pathways of the causative parasites. For leishmaniasis, the targets such as nucleoside analogs, inhibitors targeting nucleoside phosphate kinases of the parasite’s purine salvage pathway, 20S proteasome of Leishmania, mitochondria, and the associated proteins are reviewed along with the chemical structures of potential drug candidates. Similarly, in case of therapeutics for Chagas disease, several target-based drug candidates targeting sterol biosynthetic pathway (C14-ademethylase), L-cysteine protease, heme peroxidation, mitochondria, farnesyl pyrophosphate, etc., which are vital and unique to the causative parasite are discussed. Moreover, the use of nano-based formulations towards the therapeutics of the above diseases is also discussed.

The photophysical properties of tris(polypyridyl)ruthenium(II) complex [Ru(dmbpy)3]2+ [dmbpy = 4,4′-dimethyl-2,2′-bipyridine] were investigated and compared with [Ru(bpy)3]2+ following both experimental and computational approaches. The variations in the electronic properties of the complex in the ground and excited states were determined by density functional theory (DFT) methods, and their effects on the anticancer, antioxidant, and antimicrobial activities were also evaluated by molecular docking and dynamic simulation studies. The potential of these complexes to serve as bioanalytes was investigated by their ability to bind with quinones, the well-known electron mediators in numerous light-driven reactions. Following the above, the anticancer properties were evaluated against breast cancer-related proteins. The results revealed that the complex possesses comparable anticancer and antioxidant potential to that of [Ru(bpy)3]2+. The physical, electronic, and biological properties of this complex depend on the nature of the ligands and the medium of investigation. Herein, the potential applications of [Ru(bpy)3]2+ in clinical diagnostics as antioxidants and therapeutic agents were evaluated. [ABSTRACT FROM AUTHOR]

Heterocyclic molecules, containing nitrogen, sulphur, oxygen, etc., have proven their significant roles in drug discovery. Mycobacterium tuberculosis has been one long-lasting disease for several decades and to date this disease, particularly those with multidrug resistance does not have highly efficient and potent therapeutics. The role of the methylcitrate cycle in detoxifying propionyl-CoA, a product formed from the metabolism of host cholesterol by Mtb is well known. Therefore, inhibiting key enzymes or pathways involved in this cycle could potentially influence the survival of the pathogen. Herein a small library of 16 new (Thiazinan-2-ylidene)pyridine-2-amine derivatives is investigated for their potential as anti-tuberculosis inhibitors via various computational methods like docking, dynamic simulations and ADME (absorption, distribution, metabolism and excretion). Further evaluations were carried out with online machine learning tools – mycoCSM and PAINS. [ABSTRACT FROM AUTHOR]

The Click reaction that involves Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) serves as the most potent and highly dependable tool for the development of many complex architectures. It has paved the way for the synthesis of numerous drug molecules with enhanced synthetic flexibility, reliability, specificity and modularity. It is all about bringing two different molecular entities together to achieve the required molecular properties. The utilization of Click chemistry has been well demonstrated in organic synthesis, particularly in reactions that involve biocompatible precursors. In pharmaceutical research, Click chemistry is extensively utilized for drug delivery applications. The exhibited bio-compatibility and dormancy towards other biological components under cellular environments makes Click chemistry an identified boon in bio-medical research. In this review, various click-derived transition metal complexes are discussed in terms of their applications and uniqueness. The scope of this chemistry towards other streams of applied sciences is also discussed. [ABSTRACT FROM AUTHOR]

Mining operations demand accurate 3D geological models for resource estimation and production. The industry-wide accepted method for constructing such domains is to use exploration-based wireframes, limiting the accuracy of the domains by the sparsity of the exploration holes. Update of the domains using blast-hole data is highly desirable to increase the accuracy of the models and enable better decision making for downstream mining processes. We discuss some of the practical and theoretical problems of using existing boundaries created using exploration drill-hole data. We also propose using the blast-hole data to adjust ore to waste boundaries. The proposed methodology is evaluated on a dataset from an iron ore deposit located in the Brockman Iron Formation of the Hamersley Province, Western Australia, demonstrating important changes in multiple boundaries in this real-world mining dataset. [ABSTRACT FROM AUTHOR]

With an alarming increase in the number of cancer patients and a variety of tumors, it is high time for intensive investigation on more efficient and potent anti-tumor agents. Though numerous agents have enriched the literature, still there exist challenges, with the availability of different targets and possible cross-reactivity. Herein we have chosen the phosphoinositide 3-kinase (PI3K) as the target of interest and investigated the potential of pyrido fused imidazo[4,5-c]quinoline derivatives to bind strongly to the active site, thereby inhibiting the progression of various types of tumors. The AutoDock, Glide and the Prime-MM/GBSA analysis are used to execute the molecular docking investigation and validation for the designed compounds. The anti-tumor property evaluations were carried out by using PASS algorithm. Based on the GLIDE score, the binding affinity of the designed molecules towards the target PI3K was evaluated. The energetics associated with static interactions revealed 1j as the most potential candidate and the dynamic investigations including RMSD, RMSF, Rg, SASA and hydrogen bonding also supported the same through relative stabilization induced through ligand interactions. Subsequently, the binding free energy of the Wortmannin and 1j complex calculated using MM-PBSA analysis. Further evaluations with PASS prediction algorithm also supported the above results. The studies reveal that there is evidence for considering appropriate pyrido fused imidazo[4,5-c]quinoline compounds as potential anti-tumor agents.

Crosslinking of proteins has gained immense significance in the fabrication of biomaterials for various health care applications. Various novel chemical-based strategies are being continuously developed for intra-/inter-molecular crosslinking of proteins to create a network/matrix with desired mechanical/functional properties without imparting toxicity to the host system. Many materials that are used in biomedical and food packaging industries are prepared by chemical means of crosslinking the proteins, besides the physical or enzymatic means of crosslinking. Such chemical methods utilize the chemical compounds or crosslinkers available from natural sources or synthetically generated with the ability to form covalent/non-covalent bonds with proteins. Such linkages are possible with chemicals like carbodiimides/epoxides, while photo-induced novel chemical crosslinkers are also available. In this review, we have discussed different protein crosslinking strategies under chemical methods, along with the corresponding crosslinking reactions/conditions, material properties and significant applications.

A bacterial strain was isolated from tannery effluent which can tolerate high concentrations of potassium dichromate up to 1000 ppm. The isolated microorganism was identified as Pseudomonas aeruginosa by performing biochemical tests and molecular characterization. In the presence of excess of carbohydrate source, which is a physiological stress, this strain produces Polyhydroxybutyrate (PHB). This intracellular polymer, which is synthesized, is primarily a product of carbon assimilation and is employed by microorganisms as an energy storage molecule to be metabolized when other common energy sources are limitedly available. Efforts were taken to check whether the PHB has any positive effect on spent wash decolorization. When a combination of PHB and the isolated bacterial culture was added to spent wash, a maximum color removal of 92.77% was found which was comparatively higher than the color removed when the spent wash was treated individually with the PHB and Pseudomonas aeruginosa. PHB behaved as a support material for the bacteria to bind to it and thus develops biofilm, which is one of the natural physiological growth forms of microorganisms. The bacterial growth in the biofilm and the polymer together acted in synergy, adsorbing and coagulating the pollutants in the form of color pigments. [ABSTRACT FROM AUTHOR]