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Based on unselectively, several side effects and drug resistance of available anticancer agents, the development and research for novel anticancer agents is necessary. In this study, a new series of quinazoline-4(3H)-one derivatives having a thiol group at position 2 of the quinazoline ring (8a-8 h) were designed and synthesized as potential anticancer agents. The Chemical structures of all compounds were characterized by 1H-NMR, 13C-NMR, and Mass spectroscopy. The antiproliferative activity of all derivatives were determined against two cancer cell lines (MCF-7 and SW480) and one normal cell lines (MRC-5) by the MTT method. Cisplatin, Erlotinib and Doxorubicin were used as positive controls. The results of in vitro screening showed that 8a with an aliphatic linker to SH group was the most potent compound with IC50 values of 15.85 ± 3.32 and 17.85 ± 0.92 µM against MCF-7 and SW480 cell lines, respectively. 8a indicated significantly better potency compared to Erlotinib in the MCF-7 cell line. The cytotoxic results obtained from testing compound 8a on the normal cell line, revealing an IC50 value of 84.20 ± 1.72 µM, provide compelling evidence of its selectivity in distinguishing between tumorigenic and non-tumorigenic cell lines. Structure–activity relationship indicated that the variation in the anticancer activities of quinazoline-4(3H)-one derivatives was affected by different substitutions on the SH position. Molecular docking and MD simulation were carried out for consideration of the binding affinity of compounds against EGFR and EGFR-mutated. The binding energy of compounds 8a and 8c were calculated at -6.7 and − 5.3 kcal.mol− 1, respectively. Compounds 8a and 8c were found to establish hydrogen bonds and some other important interactions with key residue. The DFT analysis was also performed at the B3LYP/6–31 + G(d, p) level for compounds 8a, 8c and Erlotinib. Compound 8a was thermodynamically more stable than 8c. Also, the calculated theoretical and experimental data for the IR spectrum were in agreement. The obtained results delineated that the 8a can be considered an appropriate pharmacophore to develop as an anti-proliferative agent. [ABSTRACT FROM AUTHOR]

Graphene oxide modified with tryptophan (GO-Trp) has been introduced as a new heterogeneous acid-base biocatalyst for synthesis of some pyran derivatives. GO was prepared according to the Hummer's method and tryptophan as a low-cost green amino acid is covalently bonded to the surface of GO without any organic or toxic reagents in a green way. The new catalyst was characterized by different spectroscopic methods such as Fourier transform infrared, X-ray diffraction (XRD), etc. .... The results of XRD patterns showed an increase in the distance between the GO plates in the presence of the modifying agent which specifies the presence of amino acid between the GO layers. XPS analysis also confirmed successful modification through the presence of C–N bonds in the structure of the catalyst. In addition, improvements in thermal stability and changes in the morphology of the samples were observed using thermogravimetric analysis and Field emission scanning electron microscopy analysis respectively. Evaluation of the catalyst performance in the synthesis of some benzo[b]pyran and pyrano[3,2-c] chromene derivatives showed presentable results. Seven benzo[b]pyran (4a–4g) and five pyrano[3,2-c] chromene (4h–4l) derivatives were synthesized. GO-Trp as a safe, natural and efficient catalyst, could be reused up to 5 runs for synthesis of pyran derivatives without any significant decrease in its potency. High purity of the products and desirable yields are other points that make the present work more attractive. [ABSTRACT FROM AUTHOR]

Thirteen novel isatin‐ampyrone Schiff bases derivatives were synthesized in only two steps of 70%–90% overall yields. In vitro cytotoxic activity of these new Schiff bases against three human tumor cell lines (MCF‐7, A549, and SCOV3) as well as normal breast cell line (MCF‐10A) were evaluated by MTT assay. Structure–activity relationship of the tested compounds revealed that chlorine group at C‐5 position of the isatin ring significantly increased the cytotoxic activity. This study generally led to introduce a highly active molecule (M12) with IC50 values of 5.12, 25.5, and 12.9 μΜ, on MCF‐7, A549, and SCOV3, respectively. Furthermore, molecular docking studies of the synthesized compounds were also done to investigate their binding modes towards VEGFR‐2 and JNK3‐MAP kinase as the main targets for isatin‐containing anticancer agents. Binding free energy values of the compounds showed positive correlation with their cytotoxic activities. To confirm the docking results, molecular docking simulations of potent compound (M12) against VEGFR‐2 and JNK3 MAP kinase were also performed. According to the cytotoxic results and in silico ADMET predictions together, M12 can be considered as a potent candidate for the future anticancer studies. [ABSTRACT FROM AUTHOR]

A series of 2-aryl/alkyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazines (S1–S11) were synthesized with an eco-friendly and recoverable nanocatalyst (GO-Fe3O4–Ti(IV)) as an efficient magnetic composite. The new nanocatalyst was characterized by FT-IR, XRD and, EDS analysis. A conformable procedure, easy to work up and having a short reaction time with high yields are some advantages of this method. The new catalyst is also thermal-stable, reusable and, environment-friendly. The chemical structures of the synthesized 1,3-oxazine compounds were confirmed by comparing their melting points with those reported in literature. Then, the anticonvulsant activity of these compounds was assessed by the intraperitoneal pentylenetetrazole test (ipPTZ). Compounds S10 and S11 displayed considerable activity against chemically-induced seizure tests. The molecular simulation was also done to achieve their binding affinities as γ‐aminobutyric acid A (GABA‐A) receptor agonists as an assumptive mechanism of their anticonvulsant action. The result of molecular studies represented strongly matched with biological activity. Molecular docking simulation of the potent compound (S10) and diazepam as the positive control was performed and some critical residues like Thr262, Asn265, Met286, Phe289, and Val290 were identified. Based on the anticonvulsant results and also in silico ADME predictions, S11 can be to become a potential drug candidate as an anticonvulsant agent. [ABSTRACT FROM AUTHOR]

In recent years, resistance to conventional antimicrobial drugs has become a serious concern in the clinic. Hence, the discovery of novel and effective antimicrobial agents with improved properties is of great value. In this study, the antibacterial and anticandidal activities of some imidazole, benzimidazole and benztriazole derivatives (C1-C8) against several species of Gram-positive and Gram-negative bacteria, including Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli and Salmonella typhi as well as one species of fungi including Candida albicans, were evaluated using Clinical & Laboratory Standards Institute (CLSI) method. Antimicrobial evaluation revealed that among the tested compounds, imidazole derivative (C5) indicated the highest activity against bacterial strains and Candida albicans. It was found that compound C5 is more potent than ampicillin against S. aureus strain (MIC =2-16 µg/mL) and possessed excellent anticandidal activity (MIC =1 µg/mL) which was comparable to Amphotericin B as the positive control. In addition, cytotoxic activity of the tested compounds was investigated using MTT assay. The results of MTT assay demonstrated that the toxicity of the tested compounds was less than 35%. [ABSTRACT FROM AUTHOR]

Oxindoles and spirooxindoles as poly-functionalized heterocycles are important synthetic targets because of their biological activity and applications to pharmaceutical guide discovery. The spirooxindole structure is usually found in a variety of complex alkaloids and many compounds that possess biological activity. In this study, we have proposed an easy and efficient access to spirooxindole from N-alkylated isatin derivatives, an activated methylene and 4-hydroxycumarin to get such compounds powerfully and suitably. Here we synthesized 18 new derivatives (4a–4r) of spirooxindoles by multicomponent reaction method. Chemical structures of all products were confirmed by IR, 1HNMR, 13CNMR, and Mass Spectroscopy. The reaction conditions were also optimized in the point of different kinds of catalysts, temperature, and solvents. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is the most prevalent neurodegenerative disorder characterized by significant memory loss and cognitive impairments. Studies have shown that the expression level and activity of the butyrylcholinesterase enzyme increases significantly in the late stages of Alzheimer's disease, so butyrylcholinesterase can be considered as a promising therapeutic target for potential Alzheimer's treatments. In the present study, a novel series of 2,4-disubstituted quinazoline derivatives (6a-j) were synthesized and evaluated for their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinestrase (BuChE) enzymes, as well as for their antioxidant activities. The biological evaluation revealed that compounds 6f, 6h, and 6j showed potent inhibitory activities against eqBuChE, with IC 50 values of 0.52, 6.74, and 3.65 µM, respectively. These potent compounds showed high selectivity for eqBuChE over eelAChE. The kinetic study demonstrated a mixed-type inhibition pattern for both enzymes, which revealed that the potent compounds might be able to bind to both the catalytic active site and peripheral anionic site of eelAChE and eqBuChE. In addition, molecular docking studies and molecular dynamic simulations indicated that potent compounds have favorable interactions with the active sites of BuChE. The antioxidant screening showed that compounds 6b, 6c, and 6j displayed superior scavenging capabilities compared to the other compounds. The obtained results suggest that compounds 6f, 6h, and 6j are promising lead compounds for the further development of new potent and selective BuChE inhibitors., (© 2024. The Author(s).)

Background: Azoles are the famous and widespread scaffold in the pharmaceutical industry due to their wide range of activities, high efficacy, good tolerability, and oral availability. Furthermore, azole derivatives have attracted attention as potent antimicrobial agents., Introduction: The purpose of this review is to provide an overview of pharmacological aspects of the main scaffolds of azoles, including imidazole, benzimidazole, triazole, and tetrazole, which possess antimicrobial activity, reported from 2016 to 2020, as well as all of our publication in this field. In addition, we discuss the relationship between structure and activity and molecular docking studies of the azole derivatives to provide critical features and valuable information for the synthesis of novel azole compounds with desirable biological activities. The presented structures in this review have been tested against several bacteria and fungi, such as E. coli and C. albicans, which have been common in all of these studies., Results: A comparison of the reported MIC for tested compounds showed fluconazole base structures as the most active antifungal agents, and triazole derivatives bearing nitrophenyl and coumarin moieties to have the most dominant antibacterial activity., Conclusion: Triazole and imidazole scaffolds are more important for designing antimicrobial compounds than other azole derivatives, like benzimidazole or tetrazole. All the most active compounds were observed to fulfill the Lipinski rule., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)