In the current study, new thienopyrimidine conjugates bearing 1,2,3-triazole core and different sugar moieties have been designed and synthesized by Cu(I)-catalysed click dipolar cycloaddition. The cytotoxic activity of the synthesised conjugates 2, 5, 7, and 13–18 was studied against HCT-116 and MCF-7 cell lines by the MTT assay. The triazole glycosides 16 and 18 provided significant cytotoxic activities against HCT-116 cell lines comparable to that of doxorubicin and other studied compounds. The cytotoxic behaviour against MCF-7 exhibited that all the investigated compounds were more potent than doxorubicin. Moreover, all screened targets were evaluated against mutant EGFR kinase type L858R and the results revealed that the acetylated 1,2,3-triazole glycosides 13–18 exhibited excellent EGFR inhibitory activity in comparison with gefitinib. Furthermore, molecular modelling studies were performed to investigate the binding affinity of the most active compounds to EGFR enzyme.

Alzheimer’s disease (AD) is a chronic dysfunction of neurons in the brain leading to dementia. It is characterized by gradual mental failure, abnormal cognitive functioning, personality changes, diminished verbal fluency, and speech impairment. It is caused by neuronal injury in the cerebral cortex and hippocampal area of the brain. The number of individuals with AD is growing at a quick rate. The pathology behind AD is the progress of intraneuronal fibrillary tangles, accumulation of amyloid plaque, loss of cholinergic neurons, and decrease in choline acetyltransferase. Unfortunately, AD cannot be cured, but its progression can be delayed. Various FDA-approved inhibitors of cholinesterase enzyme such as rivastigmine, galantamine, donepezil, and NDMA receptor inhibitors (memantine), are available to manage the symptoms of AD. An exhaustive literature survey was carried out using SciFinder’s reports from Alzheimer’s Association, PubMed, and Clinical Trials.org. The literature was explored thoroughly to obtain information on the various available strategies to prevent AD. In the context of the present scenario, several strategies are being tried including the clinical trials for the treatment of AD. We have discussed pathophysiology, various targets, FDA-approved drugs, and various drugs in clinical trials against AD. The goal of this study is to shed light on current developments and treatment options, utilizing phytopharmaceuticals, nanomedicines, nutraceuticals, and gene therapy.

Thiosemicarbazones and their transition metal complexes are biologically active compounds and anticancer agents with versatile structural properties. In this contribution, the structural features and stability of four pyridoxal-thiosemicarbazone (PLTSC) complexes with Fe, Co, Ni, and Cu were investigated using the density functional theory and natural bond orbital approach. Special emphasis was placed on the analysis of the donor atom−metal interactions. The geometry of compounds and crystallographic structures were further examined by Hirshfeld surface analysis, and the main intermolecular interactions were outlined. It has been shown that the geometry and the number of PLTSC units in the structure determine the type and contribution of the specific interactions. The binding of all four complexes to bovine and human serum albumin was investigated through spectrofluorometric titration. The dependency of the thermodynamic parameters on the present metal ion and geometry was explained by the possible interactions through molecular docking simulations. The binding of complexes to DNA, as one of the possible ways the compounds could induce cell death, was examined by molecular docking. The cytotoxicity was measured towards HCT116, A375, MCF-7, A2780, and MCF5 cell lines, with Cu-PLTSC being the most active, as it had the highest affinity towards DNA and proteins.

Diabetes is a significant global health concern that increases the vulnerability to various chronic illnesses. In view of this issue, the current research aimed to examine the effects of administering an extract derived from the tubers of Cyperus rotundus L (CrE) on obesity, type 1 diabetes, and liver-kidney toxicity. Through the utilization of HPLC-DAD analysis, it was discovered that the extract contained several components, including quercetin (47.8%), luteolin glucoside (17%), luteolin (7.56%), apigenin-7-glucoside (6.29%), naringinin (4.52%), and seven others. In vitro experiments they have demonstrated that CrE effectively inhibited key digestive enzymes associated with obesity and type 2 diabetes, such as DPP-4, PTP1B, lipase, and α-amylase, as evidenced by their respective IC50 values are about 23, 51,83, and 67 μg/ml respectively. Furthermore, when diabetic rats were administered CrE, the activity of pancreatic enzymes linked to inflammation, namely 5-lipoxygenase (5-LO), hyaluronidase (HAase), and myeloperoxidase (MPO), was significantly suppressed by 48, 41, 75, and 47%, respectively. Moreover, CrE exhibited protective effects on pancreatic β-cells by inhibiting the formation of thiobarbituric acid reactive substances (TBARS) by 65% and the induction of superoxide Dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities by 62, 108, and 112% respectively as compared to diabetic untreated rat. Additionally, CrE significantly inhibited the activities of intestinal, pancreatic, and serum lipase and α-amylase activities. In diabetic rats, CrE administration suppressed glycogen phosphorylase (GP) stimulated glycogen synthase (GS) activities by 45 and 30%; and this increased liver glycogen content by 45%. Furthermore, CrE modulated key hepatic enzymes involved in carbohydrate metabolism, including hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase (G6P), and fructose-1,6-bisphosphatase (FBP). Notably, the average food and water intake (AFI and AWI) of diabetic rats treated with CrE was reduced by 15 and 16% respectively as compared to those without any treatment. Therefore, this study demonstrated the effectiveness of Cyperus rotundus tubers in preventing and treating obesity and diabetes.

In a sustained search for novel potential drug candidates with multispectrum therapeutic application, a series of novel spirooxindoles was designed and synthesized via regioselective three-component reaction between isatin derivatives, 2-phenylglycine and diverse arylidene-imidazolidine-2,4-diones (Hydantoins). The suggested stereochemistry was ascertained by an X-ray diffraction study and NMR spectroscopy. The resulting tetracyclic heterocycles were screened for their in vitro and in vivo anti-inflammatory and analgesic activity and for their in vitro antimicrobial potency. In vitro antibacterial screening revealed that several derivatives exhibited remarkable growth inhibition against different targeted microorganisms. All tested compounds showed excellent activity against the Micrococccus luteus strain (93.75 µg/mL ≤ MIC ≤ 375 µg/mL) as compared to the reference drug tetracycline (MIC = 500 µg/mL). Compound 4e bearing a p-chlorophenyl group on the pyrrolidine ring exhibited the greatest antifungal potential toward Candida albicans and Candida krusei (MIC values of 23.43 µg/mL and 46.87 µg/mL, respectively) as compared to Amphotericin B (MIC = 31.25 and 62.50 µg/mL, respectively). The target compounds were also tested in vitro against the lipoxygenase-5 (LOX-5) enzyme. Compounds 4i and 4l showed significant inhibitory activity with IC₅₀ = 1.09 mg/mL and IC₅₀ = 1.01 mg/mL, respectively, more potent than the parent drug, diclofenac sodium (IC₅₀ = 1.19 mg/mL). In addition, in vivo evaluation of anti-inflammatory and analgesic activity of these spirooxindoles were assessed through carrageenan-induced paw edema and acetic acid-induced writhing assays, respectively, revealing promising results. In silico molecular docking and predictive ADMET studies for the more active spirocompounds were also carried out.