Morteza Mehrdad

Alzheimer’s disease (AD) is a degenerative neurological disorder that chronically and irreversibly affects memory, cognitive function, learning ability, and organizational skills. Numerous studies have demonstrated BACE1 as a critical therapeutic target for AD, emphasizing the need for specific inhibition of BACE1 to develop effective therapeutics. However, current BACE1 inhibitors have certain limitations. Therefore, the aim of this study was to identify potential novel candidates derived from natural products that can be utilized for the treatment of AD. To achieve this, 80,617 natural compounds from the ZINC database were subjected to virtual screening and subsequently filtered according to the rule of five (RO5), leading to the identification of 1,200 compounds. Subsequently, the 1,200 compounds underwent molecular docking studies against the BACE1 receptor, utilizing high-throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP) techniques to identify high-affinity ligands. Of the 50 ligands that exhibited the highest G-Scores in HTVS, further analysis was conducted using SP docking and scoring methods. This analysis led to the identification of seven ligands with enhanced binding affinities, which were then subjected to additional screening via XP docking and scoring. Finally, the stability of the most promising ligand in relation to BACE1 was assessed through molecular dynamics (MD) simulations. The computational screening demonstrated that the docking energy values for seven ligands binding to target enzymes ranged between − 6.096 and − 7.626 kcal/mol. Among these, ligand 2 (L2) exhibited the best binding energy at -7.626 kcal/mol with BACE1. MD simulations further confirmed the stability of the BACE1-L2 complex, emphasizing the formation of a robust interaction between L2 and the target enzymes. Additionally, pharmacokinetic and drug-likeness evaluations indicated that L2 is non-carcinogenic and able to permeate the blood-brain barrier (BBB). The findings of this study will contribute to narrowing down the selection of candidates for subsequent in vitro and in vivo testing.

This paper describes the development of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate compound as a heterocyclic enols containing a Michael acceptor so that it participates in an Ugi-type multicomponent condensation through a Smiles rearrangement in replacement of acid components. The new four-component containing 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate, aldehyde derivatives, amine derivatives and isocyanides process leads readily and efficiently to heterocyclic enamines. This report is an outstanding strategy for the preparation of new biologically structures containing peptidic or pseudo-peptidic with quinolin-2(1H)-one scaffolds. Graphical abstract

Quinazoline‐2,4(1H,3H)‐dione is a significant class of N‐fused heterocyclic with a wide range of biological functions, including anti‐HIV, anticancer, antifungal, antibacterial, antimutagenic, anticoccidial, anticonvulsant, anti‐inflammatory, antidepressant, antimalarial, antioxidant, antileukemic, and antileishmanial activities, and other activities, and has attracted great attention in organic and medicinal chemistry. As a result, all chemists and pharmaceutical chemists must be aware of many methods to make quinazoline‐2,4(1H,3H)‐dione. This review paper focuses on various methods for producing quinazoline‐2,4(1H,3H)‐diones, such as green methods and homogeneous or heterogeneous catalysts from various precursors under varied conditions.

The antibacterial properties of CFO/BiOI nanocomposite were investigated in our current study because of their importance in Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Bacillus cereus. MIC, MBC, Disk Diffusion, and IC50 tests cefalotin (CF), amoxicillin (AMX), gentamicin (GM), Trimethoprim‐sulphamethoxazole (SXT), and Ceftriaxone (CRO) antibiotics in concentration 30, 10, 10, 25, and 30 were used, respectively. Various techniques such as X‐ray diffraction (XRD), scanning electron microscope (SEM), high‐resolution mapping, and energy dispersive X‐ray spectroscopy (EDAX) have been used to determine the properties of produced nanocomposites. The results showed CFO/BiOI nanocomposite exhibits strong significant biological activity against B. cereus. The results of MBC (minimum bactericidal concentration) and MIC (Minimum Inhibition Concentration) tests for CFO/BiOI nanocomposites on bacteria were examined in the range of 0.12–0.48 and 0.06 to 0.24 mg ml⁻¹, respectively. According to the results,, the minimum IC50 value was determined at a concentration of 0.061 mg ml⁻¹. On the other hand, the most resisting and susceptible bacteria in this method were P. aeruginosa and B. cereus, respectively. These findings are identical to a prior study on antibacterial properties of CoFe₂O₄ nanoparticles. The MBC endpoint is defined as the lowest concentration, which killed 98% of the bacterial population.

Candida albicans is a pathogenic opportunistic yeast found in the human gut flora. It may also live outside of the human body, causing diseases ranging from minor to deadly. Candida albicans begins as a budding yeast that can become hyphae in response to a variety of environmental or biological triggers. The hyphae form is responsible for the development of multidrug resistant biofilms, despite the fact that both forms have been associated to virulence Here, we have proposed a linear and SPA-linear quantitative structure activity relationship (QSAR) modeling and prediction of Candida albicans inhibitors. A data set that consisted of 60 derivatives of benzoxazoles, benzimidazoles, oxazolo (4, 5-b) pyridines have been used. In this study, that after applying the leverage analysis method to detect outliers’ molecules, the total number of these compounds reached 55. SPA-MLR model shows superiority over the multiple linear regressions (MLR) by accounting 90% of the Q² of anti-fungus derivatives ‘activity. This paper focuses on investigating the role of SPA-MLR in developing model. The accuracy of SPA-MLR model was illustrated using leave-one-out (LOO). The mean effect of descriptors and sensitivity analysis show that RDF090u is the most important parameter affecting the as behavior of the inhibitors of Candida albicans.

Benzylation of DBU followed by anion exchange of the resulting salt with trifluoroacetate gave nearly quantitatively the ionic liquid [Bn-DBU][TFA]. It is shown here to be an efficient catalyst for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones via the three-component reaction of phthalhydrazide, aromatic aldehydes, and active α-methylene nitriles. DFT calculations at the B3LYP/SVP level and the experimental results are in agreement with a three-step mechanism for this reaction. Based on the DFT calculations, the catalytic effect largely arises from the intrinsic ionic properties of the ionic liquid rather than its action as a simple base. These calculations also predict the existence of two close-in-energy activated complexes whose rate determining roles and energies depend on their interaction with the anionic component of the ionic liquid, as [Bn-DBU][TFA] has shown a higher catalytic activity than [Bn-DBU][OAc]. This mechanistic approach opens up new and promising insights into the rational design of ionic liquid catalysts for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones. The synthetic method presented here has several prominent advantages.