We report the synthesis and crystal structures of three new copper(II) Schiff-base complexes. The complexes have been characterized by elemental analysis and Fourier transform infrared (FT-IR) and UV–visible spectroscopies. The X-ray diffraction (XRD) analysis reveals that complexes 1 and 3 crystallize in a monoclinic space group C2/c and 2 in a triclinic space group P1̅, each adopting a square planar geometry around the metal center. We use a density functional theory method to explore the quantum chemical properties of these complexes. The calculation proceeds with the three-dimensional (3D) crystal structure characterization of the complexes in which the calculated IR and UV–vis values are comparable to the experimental results. Charge distribution and molecular orbital analyses enabled quantum chemical property prediction of these complexes. We study the drug-likeness properties and binding potentials of the synthesized complexes. The in silico outcome showed that they could serve as permeability-glycoprotein (P-gp) and different cytochrome P450 substrates. Our calculations showed that the complexes significantly bind to cytochrome P450 3A4.

Developing new, more effective antibiotics against resistant Mycobacterium tuberculosis that inhibit its essential proteins is an appealing strategy for combating the global tuberculosis (TB) epidemic. Finding a compound that can target a particular cavity in a protein and interrupt its enzymatic activity is the crucial objective of drug design and discovery. Such a compound is then subjected to different tests, including clinical trials, to study its effectiveness against the pathogen in the host. In recent times, new techniques, which involve computational and analytical methods, enhanced the chances of drug development, as opposed to traditional drug design methods, which are laborious and time-consuming. The computational techniques in drug design have been improved with a new generation of software used to develop and optimize active compounds that can be used in future chemotherapeutic development to combat global tuberculosis resistance. This review provides an overview of the evolution of tuberculosis resistance, existing drug management, and the design of new anti-tuberculosis drugs developed based on the contributions of computational techniques. Also, we show an appraisal of available software and databases on computational drug design with an insight into the application of this software and databases in the development of anti-tubercular drugs. The review features a perspective involving machine learning, artificial intelligence, quantum computing, and CRISPR combination with available computational techniques as a prospective pathway to design new anti-tubercular drugs to combat resistant tuberculosis.

As a member of the Orthomyxoviridae family of viruses, influenza viruses (IVs) are known causative agents of respiratory infection in vertebrates. They remain a major global threat responsible for the most virulent diseases and global pandemics in humans. The virulence of IVs and the consequential high morbidity and mortality of IV infections are primarily attributed to the high mutation rates in the IVs’ genome coupled with the numerous genomic segments, which give rise to antiviral resistant and vaccine evading strains. Current therapeutic options include vaccines and small molecule inhibitors, which therapeutically target various catalytic processes in IVs. However, the periodic emergence of new IV strains necessitates the continuous development of novel anti-influenza therapeutic options. The crux of this review highlights the recent studies on the biology of influenza viruses, focusing on the structure, function, and mechanism of action of the M2 channel and neuraminidase as therapeutic targets. We further provide an update on the development of new M2 channel and neuraminidase inhibitors as an alternative to existing anti-influenza therapy. We conclude by highlighting therapeutic strategies that could be explored further towards the design of novel anti-influenza inhibitors with the ability to inhibit resistant strains.

Metal compounds continued to attract diverse applications due to their malleability in several capacities. In this study, we present our findings on the crystal structures and functional properties of Ni²⁺ and Cu²⁺ complexes of N'-(2,6-dichlorophenyl)-N-mesitylformamidine dithiocarbamate (L) comprising [Ni-(L)₂] (1) and [Cu-(L)₂] (2) with a four-coordinate metal center. We established the two complex structures through ¹H and ¹³C nuclear magnetic resonance (NMR), elemental, and single-crystal X-ray analysis. The analyses showed that the two complexes are isomorphous, having P2₁/c as a space group and a unit-cell similarity index (π) of 0.002. The two complexes conform to a distorted square planar geometry around the metal centers. The calculated and experimental data, including bond lengths, angles, and NMR values, are similar. Hirshfeld surface analysis revealed the variational contribution of the different types of intermolecular contacts driven by the crystal lattice of the two solvated complexes. Our knowledge of the potential biological implication of these structures enabled us to probe the compounds as prospective CYP3A4 inhibitors. This approach mimics current trends in pharmaceutical design and biomedicine by incorporating potentially active molecules into various media to predict their biological efficacies. The simulations show appreciable binding of compounds 1 and 2 to CYP3A4 with average interaction energies of –97 and –87 kcal/mol, respectively. The protein attains at least five conformational states in the three studied models using a Gaussian Mixture Model-based clustering and free energy prediction. Electric field analysis shows the crucial residues to substrate binding at the active site, enabling CYP3A4 structure to function prediction. The predicted inhibition with these Ni²⁺ and Cu²⁺ complexes indicates that CYP3A4 overexpression in a diseased state like cancer would reduce, thereby increasing the chemotherapeutic compounds' shelf-lives for adsorption. This multidimensional study addresses various aspects of molecular metal electronics, including their application as substrate-mimicking inhibitors. The outcome would enable further research on bio-metal compounds of critical potential.