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Prostate carcinoma is one of the most commonly diagnosed visceral malignancies and the fifth leading cause of cancer-related mortality in males. Reportedly, a series of dietary lipids are identified as 1-cis-4-cis-pentadiene polyunsaturated fatty acids (PUFAs), which play a dominant role in prostate carcinogenesis. Four species of human lipoxygenases (LOXs), a family of nonheme iron-containing enzymes, mediate the deoxygenation of the aforementioned PUFAs. 15-LOX-1 in particular metabolizes the ω -6 lipids and generates certain metabolites (e.g., 13-(S)-hydroxyoctadecaenoic acid) which results in vascular homeostasis, cell proliferation and tissue differentiation in the prostate. Furthermore, in prostate cancer (PCa), the expression of 15-LOX-1 is elevated and positively correlated with the Gleason score of the tumor (an indicator of the disease severity). As membrane receptors, kinases and transcriptional factors are all affected by carcinogenic signals of 15-LOX-1, therapeutic agents that directly inhibit this enzyme can be advantageous in the treatment of PCa. To our knowledge, there are limited effective treatments for PCa, and there is no therapy for its metastatic condition. In this respect, 15-LOX-1, as an appropriate candidate for drug development, was subjected to homology modeling, phylogenic assessment, cross-docking analysis and molecular dynamics (MD) simulation to identify an eligible inhibiting agent amongst a library of 30 potential targeting compounds for PCa management. Prostate carcinoma is one of the most commonly diagnosed visceral malignancies and the fifth leading cause of cancer-related mortality in males. To our knowledge, there are limited effective treatments for prostate cancer. In this respect, human 15-Lipoxygenase-1 (15-LOX-1), as an appropriate candidate, was subjected to in-silico explorations. We report the potential for using 15-LOX-1 inhibitors, such as CHEMBL1270113, as a therapeutic approach to restore the balance between the function of lipoxygenase family members and inflammatory mediators. [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]