Mohammad Bayat

Myeloid cell leukemia-1 (Mcl-1) is a key anti-apoptotic protein that drives resistance to chemotherapy, making it a critical oncology target.

Cancer is the second leading cause of death worldwide. Main problem in current cancer therapy strategies is resistance to anti-cancer drugs and side effects. Therefore, the design of new compounds with high anticancer activity and low toxicity toward normal cells is highly desirable. In the present study, we focused on the development of novel spiropyran derivatives. A practical one-pot synthetic method was developed for preparation of spiroindenopyridotriazinepyrans containing pyranopyridine, and triazine constituent units within a unified molecular framework. This method employs readily accessible starting materials, proceeds under mild conditions, and affords products that can be purified without chromatographic techniques. The structures of the products were confirmed by NMR, IR, and mass spectrometry. Moreover, we explored the anticancer effects of related products against human pancreatic cancer cells (Panc1), human breast cancer cells (MDA-MB-231) and normal cells HDF (human dermal fibroblast) by using MTT assay and DAPI staining. Our results revealed that 9d, 9e, and 9f compounds have the highest cytotoxic activity on different cancer cells. It seems that these synthetic compounds may be a promising candidate to design therapeutic agents against different cancers.

Thioketene acetals, ketene aminals, and ketene N,S ‐acetals, particularly those bearing an electron‐withdrawing group at the α ‐position, serve as valuable synthons for the construction of heterocyclic compounds. These motifs occur in a wide range of natural and synthetic products, many of which display notable pharmacological and other biological activities. Owing to their unique electronic properties, they undergo diverse transformations, including heterocyclization, 1,4‐addition, dimerization, nucleophilic substitution, and annulation. Such reactions can be carried out under various conditions, ranging from one‐pot and multi‐component strategies to catalyzed, uncatalyzed, and light‐mediated processes. This review summarizes recent reactions involving the synthesis and applications of ketene acetals, with a particular focus on studies published between 2020–2024, and discusses their applications in modern organic synthesis.

Spirooxindole compounds have attracted considerable research interest due to their distinctive structural features and remarkable biological properties. In recent years, a wide range of synthetic strategies has been developed to construct spirooxindoles, particularly those featuring a spiro-carbon Linked to diverse Heterocyclic or carbocyclic frameworks, further enhancing their importance. Given the breadth of these synthetic approaches, a comprehensive review is crucial to providing a systematic overview of the field and facilitate access to various methodologies. This review provides a thorough analysis of current developments in spirooxindole synthesis, covering research published from 2020 to 2024. The classification is organized into four main sections based on the size of the ring attached to the spiro-carbon: three-membered, five-membered, six-membered, and seven-membered rings. These rings may be carbocyclic or may contain one or two heteroatoms, such as nitrogen, oxygen, or sulfur, further influencing the diversity of synthetic strategies and the properties of the resulting spirooxindoles. Graphical abstract

A simple and highly chemoselective heteroannulation protocol for the synthesis of polysubstituted heterocycles is reported. In this work, various oxa-aza[3.3.3]propellanes were synthesized via a sequential one-pot reaction of ninhydrin, malononitrile and nitroketene acetal or nitroketene aminals in water at ambient temperature. This successive Knoevenagel condensation/Michael addition/cyclization sequence features high atom economy, excellent efficiency, and the use of water as a solvent without the need for metal catalysts or external activators. This method can be presented as a good example of group-assisted purification (GAP), in which traditional purification techniques such as recrystallization and column chromatography are avoided and pure products are obtained simply by washing the crude products.

We synthesized a series of novel thiazoloquinolinone derivatives, achieving moderate to high yields ranging from 74 to 96%, and assessed their efficacy against Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) using in silico methodologies. The structures of these compounds were characterized through various spectroscopic techniques, including 1H-NMR, 13C-NMR, IR, and mass spectrometry. Comprehensive computational analyses, encompassing molecular docking, molecular dynamics (MD) simulations, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling, were conducted. Docking studies with VEGFR-2 revealed that all synthesized compounds exhibited docking scores between − 3.24 and − 6.63, indicating varying degrees of binding affinity. Notably, compound (5e) demonstrated the strongest binding affinity with an energy of − 6.63 kcal/mol. The MD simulations indicated that Lys868 was one of the amino acids exhibiting the highest frequency of interaction throughout the simulation. Analysis of the ADMET and physicochemical properties revealed that all inhibitor compounds possess favorable pharmacological characteristics.

A very convenient one-pot method for the synthesis of new biologically active compounds, spiro-4H-pyran derivatives, has been developed. This approach, enables the incorporation of three pharmacophoric cores: pyran, pyridine and triazine scaffolds, within a single molecular skeleton using an efficient sequential multicomponent reaction. The starting materials include ninhydrin, cyanoacetohydrazide, ethyl cyanoacetate, aromatic aldehydes, pyrazolone and malononitrile. In this process, spiropyran derivatives were produced with high efficiency through three consecutive reactions. The first step involves the synthesis of 1,6-diaminopyridinone via a three-component approach using readily available starting materials. The second step, the synthesis of pyridotriazine, occurs in a domino way without the need to separate the intermediate product of the first step. Finally, the third step involves the synthesis of new spiro-4H-pyran derivatives through a one-pot three-component reaction. This method offers several advantages, including fast and simple purification of products, the use of safe solvents, no need for metallic and toxic catalysts, high atomic economy and excellent chemoselectivity of the reactions.

Synthesized quinazolin-12-one derivatives as PDK1 inhibitors.

The epidermal growth factor receptor (EGFR), a protein located on the cell surface, belongs to the tyrosine kinase family and plays a crucial role in cell development and proliferation. Abnormal expression or mutations in the EGFR gene can lead to non–small cell lung cancer. Although established EGFR inhibitors have been effective in the treatment of cancer, they are associated with several side effects. As a result, there is an urgent need to develop novel EGFR inhibitors that can effectively target the receptor while causing no adverse side effects. In this study, a series of bis(6‐amino‐1,3‐dimethylpyrimidine‐2,4(1 H ,3 H )‐dione derivatives was synthesized in water at room temperature without the use of any catalyst, and pharmaceutical properties are investigated. Computational methods, including density functional theory (DFT), molecular docking, and molecular dynamics (MD), were utilized to investigate the chemical properties, drug‐like characteristics, and anticancer potential of the molecule. Quantum chemical calculations indicated that the molecules are relatively stable and exhibit significant electrophilic properties. The analysis of HOMO‐LUMO contour maps was conducted to illustrate charge density distributions that may be associated with biological activity. Docking studies with EGFR enzymes indicated that all compounds demonstrated favorable binding affinities, with docking scores ranging from −4.412 to −6.158 kcal/mol. Particularly, Compound 3f, with an energy of −6.158 kcal/mol, showed the best binding affinity, outperforming the native ligand, which had a docking score of −5.076 kcal/mol. The stability of the EGFR‐3f complex is significantly enhanced by the formation of five conventional hydrogen bonds and one carbon–hydrogen bond in ligand–protein interactions. MD simulations, which included analyses such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (rGyr), molecular surface area (MolSA), and polar surface area (PSA), were conducted on the EGFR‐3f complex. It was found that the EGFR‐3f complex is stable, and the results show that Compound 3f has a strong interaction with the target enzyme.

There are numerous uses for the pharmacological effects of thiazolo-pyridine and its derivatives. The main objective of the study was to synthesis 10 novel derivatives of thiazolo[3,2-a] pyridine-6,8-dicarbonitrile with a 22–78% yield, with a focus on their potential anti-diabetic properties. We investigated the interactions between these compounds and the enzyme α-amylase through an in silico study involving molecular docking. According to the docking analysis results, the resulting compounds had advantageous inhibitory properties. With a docking score of -7.43 kcal/mol against the target protein, compound 4e performed best. The stability root-mean-square deviation (RMSD) showed that the complex stabilizes after 25 ns and with minor perturbation at 80. The RMSF values of the ligand-protein complex indicate that the following residues have interacted with compound 4e during the MD simulation: Trp58, Trp59, Tyr62, Gln63, His101, Val107, lle148, Asn152, Leu162, Thr163, Gly164, Leu165, Asp197, Ala198, Asp 236, Leu237, His299, Asp300, and His305. Moreover, the pharmacokinetic and drug-like properties of the synthesized derivatives of 2-arylamino-dihydroindeno[1,2-b] pyrrol-4(1H)-one suggest that they have the potential to be effective inhibitors of α-amylase and should be considered for further research. Nevertheless, it is crucial to ascertain the in vivo and in vitro effectiveness of these compounds through biochemical and structural investigations.