Janus kinase (JAK) is a family of cytoplasmic non-receptor tyrosine kinases that includes four members, namely JAK1, JAK2, JAK3, and TYK2. The JAKs transduce cytokine signaling through the JAK-STAT pathway, which regulates the transcription of several genes involved in inflammatory, immune, and cancer conditions. Targeting the JAK family kinases with small-molecule inhibitors has proved to be effective in the treatment of different types of diseases. In the current review, eleven of the JAK inhibitors that received approval for clinical use have been discussed. These drugs are abrocitinib, baricitinib, delgocitinib, fedratinib, filgotinib, oclacitinib, pacritinib, peficitinib, ruxolitinib, tofacitinib, and upadacitinib. The aim of the current review was to provide an integrated overview of the chemical and pharmacological data of the globally approved JAK inhibitors. The synthetic routes of the eleven drugs were described. In addition, their inhibitory activities against different kinases and their pharmacological uses have also been explained. Moreover, their crystal structures with different kinases were summarized, with a primary focus on their binding modes and interactions. The proposed metabolic pathways and metabolites of these drugs were also illustrated. To sum up, the data in the current review could help in the design of new JAK inhibitors with potential therapeutic benefits in inflammatory and autoimmune diseases.

The green biosynthesis of metal nanoparticles of already explored phytomedicines has many advantages such as enhanced biological action, increased bioavailability, etc. In this direction, keeping in view the peculiar medicinal value of Tropaeolum majus L., we synthesized its silver nanoparticles (AgNPs) by adopting eco-friendly and cost-effective protocol by using methanolic and aqueous extract of T. majus . The synthesized AgNPs were characterized by using several techniques including UV spectroscopic analysis, FTIR analysis, and atomic force microscopy. The methanolic/aqueous extracts of T. majus and synthesized AgNPs were assessed for antioxidant potential and antimicrobial effect. The preliminary screening showed that the T. majus extracts have variety of reducing phytochemicals including tannins, terpenoids, flavonoids, and cardiac glycosides. The green synthesis of AgNPs was confirmed by the appearance of sharp peak at 430–450 nm in the UV-Visible spectra. The FTIR spectral analysis of extract and AgNPs exhibited that peaks at 2947.23, 2831.50, 2592.33, 2522.89, and 1,411 cm ⁻¹ disappeared in the spectra of FTIR spectra of the AgNPs, indicating carboxyl and hydroxyl groups are mainly accountable for reduction and stabilization of AgNPs. Atomic force microscopic scan of the synthesized AgNPs confirmed its cylindrical shape with size of 25 µm. The extracts and AgNPs were investigated for antioxidant potential by DPPH-free radical essay, which showed that aqueous extract has significant and dose-independent antioxidant activity; however, the synthesized AgNPs showed decline in antioxidant activity. The extracts and synthesized AgNPs were also evaluated for antibacterial activity against Klebsiella pneumonia , Staphylococcus aureus , and Bacillus subtilis. Neither extract nor AgNPs were active against Klebsiella pneumonia. The aqueous and methanolic extract exhibited inhibition against Bacillus subtilis and their synthesized AgNPs were active against Staphylococcus aureus. Our data concluded that the extracts of T. majus have necessary capping and reducing agents which make it capable to develop stable AgNPs. The aqueous extract of T. majus has potential antioxidant effect; however, the AgNPs did not enhance its free radical scavenging effect. The bacterial strains’ susceptibility of the extract and AgNPs was changed from Bacillus subtilis to Staphylococcus aureus , respectively. The biological action of AgNPs is changed in case of antibacterial activity which means that AgNPs might change the specificity of T. majus and likewise other drugs.

Non-fused ring-based OSCs are an excellent choice, which is attributed to their low cost and flexibility in applications. However, developing efficient and stable non-fused ring-based OSCs is still a big challenge. In this work, with the intent to increase V_oc for enhanced performance, seven new molecules derived from a pre-existing A–D–A type A3T-5 molecule are proposed. Different important optical, electronic and efficiency-related attributes of molecules are studied using the DFT approach. It is discovered that newly devised molecules possess the optimum features required to construct proficient OSCs. They possess a small band gap ranging from 2.22–2.29 eV and planar geometries. Six of seven newly proposed molecules have less excitation energy, a higher absorption coefficient and higher dipole moment than A3T-5 in both gaseous and solvent phases. The A3T-7 molecule exhibited the maximum improvement in optoelectronic properties showing the highest λ_max at 697 nm and the lowest E_x of 1.77 eV. The proposed molecules have lower ionization potential values, reorganization energies of electrons and interaction coefficients than the A3T-5 molecule. The V_oc of six newly developed molecules is higher (V_oc ranging from 1.46–1.72 eV) than that of A3T-5 (V_oc = 1.55 eV). Similarly, almost all the proposed molecules except W6 exhibited improvement in fill factor compared to the A3T-5 reference. This remarkable improvement in efficiency-associated parameters (V_oc and FF) proves that these molecules can be successfully used as an advanced version of terthiophene-based OSCs in the future.

Moringa oleifera Lam. (Moringaceae) is an adaptable plant with promising phytoconstituents, interesting medicinal uses, and nutritional importance. Chemical profiling of M. oleifera seeds assisted by LC-HRMS (HPLC system coupled to a high resolution mass detector) led to the dereplication of 19 metabolites. Additionally, the wound healing potential of M. oleifera seed extract was investigated in male New Zealand Dutch strain albino rabbits and supported by histopathological examinations. Moreover, the molecular mechanisms were investigated via different in vitro investigations and through analyzing the relative gene and protein expression patterns. When compared to the untreated and MEBO^®-treated groups, topical administration of M. oleifera extract on excision wounds resulted in a substantial increase in wound healing rate (p < 0.001), elevating TGF-β1, VEGF, Type I collagen relative expression, and reducing inflammatory markers such as IL-1β and TNF-α. In vitro antioxidant assays showed that the extract displayed strong scavenging effects to peroxides and superoxide free radicals. In silico studies using a molecular docking approach against TNF-α, TGFBR1, and IL-1β showed that some metabolites in M. oleifera seed extract can bind to the active sites of three wound-healing related proteins. Protein–protein interaction (PPI) and compound–protein interaction (CPI) networks were constructed as well. Quercetin, caffeic acid, and kaempferol showed the highest connectivity with the putative proteins. In silico drug likeness studies revealed that almost all compounds comply with both Lipinski’s and Veber’s rule. According to the previous findings, an in vitro study was carried out on the pure compounds, including quercetin, kaempferol, and caffeic acid (identified from M. oleifera) to validate the proposed approach and to verify their potential effectiveness. Their inhibitory potential was evaluated against the pro-inflammatory cytokine IL-6 and against the endopeptidase MMPs (matrix metalloproteinases) subtype I and II, with highest activity being observed for kaempferol. Hence, M. oleifera seeds could be a promising source of bioactive compounds with potential antioxidant and wound healing capabilities.

In the current study, unexplored type IV halogen⋯halogen interaction was thoroughly elucidated, for the first time, and compared to the well-established types I–III interactions by means of the second-order Møller–Plesset (MP2) method. For this aim, the halobenzene⋯halobenzene homodimers (where halogen = Cl, Br, and I) were designed into four different types, parodying the considered interactions. From the energetic perspective, the preference of scouted homodimers was ascribed to type II interactions (i.e., highest binding energy), whereas the lowest binding energies were discerned in type III interactions. Generally, binding energies of the studied interactions were observed to decline with the decrease in the σ-hole size in the order, C₆H₅I⋯IC₆H₅ > C₆H₅Br⋯BrC₆H₅ > C₆H₅Cl⋯ClC₆H₅ homodimers and the reverse was noticed in the case of type IV interactions. Such peculiar observations were relevant to the ample contributions of negative-belt⋯negative-belt interactions within the C₆H₅Cl⋯ClC₆H₅ homodimer. Further, type IV torsional trans → cis interconversion of C₆H₅X⋯XC₆H₅ homodimers was investigated to quantify the π⋯π contributions into the total binding energies. Evidently, the energetic features illustrated the amelioration of the considered homodimers (i.e., more negative binding energy) along the prolonged scope of torsional trans → cis interconversion. In turn, these findings outlined the efficiency of the cis configuration over the trans analog. Generally, symmetry-adapted perturbation theory-based energy decomposition analysis (SAPT-EDA) demonstrated the predominance of all the scouted homodimers by the dispersion forces. The obtained results would be beneficial for the omnipresent studies relevant to the applications of halogen bonds in the fields of materials science and crystal engineering.