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Resistance of Candida species is a major problem in the management of Candida infection. This study investigated in vivo antifungal activities of several new imidazole and triazole derivatives in a C. albicans systemic infection. The efficacy of derivatives was determined against systemic infection by C. albicans in mice with cyclophosphamide-induced immunosuppression, and the antifungal activities of the synthesized compounds were evaluated in comparison with fluconazole. Compounds 3 and 8 had the highest efficacy with minimum inhibitory concentration (MIC) values of 0.5–1 μM against the C. albicans pathogen. In vivo activities in immunosuppressed mice were also greater than fluconazole. Furthermore, docking analysis was carried out to know the binding mode of imidazole and triazole derivatives to the CYP51 active site of C. albicans and dihydrofolate reductase as a valid antifungal target. The docking study found that the antifungal results are well correlated with docking results. ADMET and in silico physicochemical parameters were also performed. This study demonstrates that compounds 3 and 8 are potential antifungal candidates against the C. albicans pathogen. [ABSTRACT FROM AUTHOR]

A novel series of diphenylquinoxaline-6-carbohydrazide hybrids 7a–o were rationally designed and synthesized as anti-diabetic agents. All synthesized compounds 7a–o were screened as possible α-glucosidase inhibitors and exhibited good inhibitory activity with IC50 values in the range of 110.6 ± 6.0 to 453.0 ± 4.7 µM in comparison with acarbose as the positive control (750.0 ± 10.5 µM). An exception in this trend came back to a compound 7k with IC50 value > 750 µM. Furthermore, the most potent derivative 7e bearing 3-fluorophenyl moiety was further explored by kinetic studies and showed the competitive type of inhibition. Additionally, the molecular docking of all derivatives was performed to get an insight into the binding mode of these derivatives within the active site of the enzyme. In silico assessments exhibited that 7e was well occupied in the binding pocket of the enzyme through favorable interactions with residues, correlating to the experimental results. [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 this paper, we report on a user-friendly synthesis of 1,4-benzodiazepine-3,5-dione derivatives via Bargellini-type reaction. The corresponding products were obtained using various 2- aminobenzamides under Bargellini reaction conditions, in good yields without unfavorable side reaction. [ABSTRACT FROM AUTHOR]

Heating isatoic anhydride with a series of primary amines at 150 °C under solvent-free conditions yielded 2-amino-N-alkylbenzamides which, in the same pot, reacted readily with chloroacetyl chloride in the presence of poly(dimethylaminoethyl acrylamide)-modified magnetic nanoparticles (MNP@PDMA), a base catalyst, to give 4-alkyl-1,4-benzodiazepine-2,5-diones in good yields without formation of by-products. [ABSTRACT FROM AUTHOR]

8 Title compounds of type (VI) are prepared by a four-component Ugi reaction followed by formation of the triazole ring by click reaction with NaN3. [ABSTRACT FROM AUTHOR]

• A novel series of carbazole-benzylpiperazine hybrids were synthesized and characterized. • The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of the synthesized compounds were evaluated. • Compounds 7a, 7e and 7k were identified as the most promising candidate for further study. • This work is helpful for researchers who planning to design and develop AChE and BuChE inhibitors. A novel series of carbazole-benzylpiperazine hybrids (7a–n) were synthesized and their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities were evaluated. The biological results indicated that the nature of linker between carbazole and benzylpiperazine moieties as well as the type of substitutions on the phenyl ring of benzylpiperazine moiety greatly affected the inhibitory activity and selectivity of the synthesized compounds towards eelAChE and eqBuChE enzymes. Among all the synthesized compounds, compounds 7a (IC 50 = 8.9 µM) and 7e (IC 50 = 5.7 µM) with fluorine substitution at meta and para positions of the phenyl ring showed the highest inhibitory activity against eelAChE and maximum inhibitory activity against eqBuChE were generated by compounds 7h (IC 50 = 5.4 µM) and 7k (IC 50 = 4.5 µM) with fluorine and methyl substitutions at meta position of the phenyl ring, respectively. Furthermore, kinetic analysis and molecular modeling studies revealed that the most active compound 7e acts as a mixed-type inhibitor against AChE, which suggested this compound interacted with both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE enzyme. [Display omitted] [ABSTRACT FROM AUTHOR]