Evidence-Based Medicine; Climbing a Mountain for a Better Decision-Making

Evidence-Based Medicine is a relatively new term used in medical sittings and Health Information Technology (HIT). It is a form of medicine that integrates practitioners’ expertise with the best available practical evidences to improve better patient care. Evidence-Based Medicine has increasingly been used and incorporated into daily medical practices to overcome the shortcomings in the conventional standard care. The purpose of this literature review is to highlight the importance of Evidence-Based Medicine and how it can act as a crucial tool in decision-making to empower the quality of medical services for better patient outcomes

Synthesis of New Azoles and Azolopyrimidines Incorporating Morpholine Moiety as Potent Anti-Tumor Agents

A new series of morpholinyl-chalcones 2a–d was prepared by reaction of 2-oxo-N,4-diarylbut-3-enehydrazonoyl chlorides 1a–d with morpholine. These chalcones were used as a building block for constructing pyrazoles 3a–d and 3,4-dihydropyrimidine-2(1H)-thione 6 via their reaction with phenylhydrazine and thiourea, respectively. Moreover, a new series of azolopyrimidine derivatives 11a,b, 15, 17, 19, and 21 incorporating morpholine moiety were synthesized by reaction of 1-morpholino-4-phenyl-1-(2-phenylhydrazono)but-3-en-2-one (2a) with a number of heterocyclic amines in the presence of a catalytic amount of acetic acid. The assigned structures for all the newly synthesized compounds were confirmed on the basis of elemental analyses and spectral data and the mechanisms of their formation were also discussed. All the synthesized compounds were tested for in vitro activities against two antitumor cell lines, human lung cancer (A-549) and human hepatocellular carcinoma (HepG-2) compared with the employed standard antitumor drug (cisplatin) and the results revealed that compounds 6, 8c and 17 have promising activities compared with cisplatin. This work is licensed under a Creative Commons Attribution 4.0 International License

Parkinson's Disease: Is It a Toxic Syndrome?

Parkinson's disease (PD) is one of the neurodegenerative diseases which we can by certainty identify its pathology, however, this confidence disappeares when talking about the cause. A long history of trials, suggestions, and theories tried linking PD to a specific causation. In this paper, a new suggestion is trying to find its way, could it be toxicology? Can we—in the future—look to PD as an occupational disease, in fact, many clues point to the possible toxic responsibility—either total or partial—in causing this disease. Searching for possible toxic causes for PD would help in designing perfect toxic models in animals

Synthesis and Biological activity of 1,3-Thiazolylidenehydrazinylidene ethylpyridiniumbromide monohydrate, 1,3-Thiazolylidenehydraziniumbromide and 1,3-Thiazolylidenehydrazine derivatives

1,3-Thiazolylidenehydrazinylidene ethylpyridinium bromide monohydrate, 1,3-thiazolylidenehydrazinium bromide and 1,3-thiazolylidenehydrazine derivatives were synthesized by heterocyclization of 2-(1-substituted ethylidene) hydrazinecarbothioamides, characterized and screened for their anti-bacterial activities. The structures of synthesized compounds were established by spectroscopic (IR, 1H, 13C-NMR, Mass) and X-ray analyses

2,7-Dimethyl-1,3-thia­zolo[4,5-d]pyridazin-4(5H)-one

The nine-membered fused-ring system of the title pyridazine derivative, C7H7N3OS, is almost planar (r.m.s. deviation 0.012 Å). In the crystal, the amino H atom forms a hydrogen bond to the ketonic O atom of a neighboring mol­ecule to generate a centrosymmetric dimer

4-(3,7-Dimethyl-4-oxo-4,5-dihydro­isoxazolo[4,5-d]pyridazin-5-yl)benzene­sulfonamide

The nine-membered fused-ring system of the title pyridazine derivative, C13H12N4O4S, is approximately planar (r.m.s. deviation 0.027 Å), and the benzene ring of the phenyl­sulfamide substituent is aligned at 43.5 (1)° to the fused-ring system. The amine group of the sulfonamide substituent forms an N—H⋯O hydrogen bond to the ketonic O atom of two neigboring mol­ecules to generate a chain running along the c axis

Quinazolin-4-one/3-cyanopyridin-2-one Hybrids as Dual Inhibitors of EGFR and BRAFV600E^{V600E}: Design, Synthesis, and Antiproliferative Activity

A novel series of hybrid compounds comprising quinazolin-4-one and 3-cyanopyridin-2-one structures has been developed, with dual inhibitory actions on both EGFR and BRAFV600E. These hybrid compounds were tested in vitro against four different cancer cell lines. Compounds 8, 9, 18, and 19 inhibited cell proliferation significantly in the four cancer cells, with GI50 values ranging from 1.20 to 1.80 µM when compared to Doxorubicin (GI50 = 1.10 µM). Within this group of hybrids, compounds 18 and 19 exhibited substantial inhibition of EGFR and BRAFV600E. Molecular docking investigations provided confirmation that compounds 18 and 19 possess the capability to inhibit EGFR and BRAFV600E. Moreover, computational ADMET prediction indicated that most of the newly synthesized hybrids have low toxicity and minimal side effects

Anti-prostate cancer metabolites from the soil-derived Aspergillus neoniveus

Prostate cancer (PCa) ranks as one of the most commonly diagnosed malignancies worldwide. Toxicity, lack of clinical efficacy, and development of resistance phenotypes are the main challenges in the control of prostate malignancies. Notably, castration-resistance prostate cancer (CRPCa) is a highly aggressive and metastatic phenotype of the disease with a poor prognosis and very limited therapeutic options. Herein, we report the isolation and genotypic identification of a soil-derived fungus Aspergillus neoniveus using the PCR-based internal transcribed spacer (ITS) region amplification approach. HPLC/MS investigation of the metabolic profile of the ethyl acetate extract from the fungal biomass revealed tentative identification of forty-five compounds belonging to various chemical classes including γ-butyrolactones, alkaloids, phenolics, and quinoids. Furthermore, the chromatographic purification of microbial extract enabled the identification of nervonic acid methyl ester (1) for the first time from endophytic fungi, as well as acetyl aszonalenin (2), and butyrolactone II (3) for the first time from A. neoniveus. The chemical frameworks of the isolated compounds were identified via extensive spectral analysis including 1 and 2D NMR and MS. The X-ray crystal structure and absolute configuration of acetyl aszonalenin (2) were also determined. Additionally, screening of in vitro anticancer activity of the fungal extract revealed its potential antiproliferative and anti-migratory activities against five different prostate cancer cells (PC3, PC-3M, DU-145, CWR-R1ca, and 22Rv1), including different cells with the castration-resistance phenotype. Moreover, the isolated metabolites significantly inhibited the proliferation, migration, and colonization of human prostate cancer cells at low micromolar levels, thus providing credence for future investigation of these metabolites in relevant anti-prostate cancer animal models. Furthermore, computational target prediction tools identified the cannabinoid G-protein coupled receptors type 1 (CB1) as a potential biological target mediating, at least in part, the anticancer effects of acetylaszonalenin (2). Moreover, molecular modeling and docking studies revealed a favorable binding pose at the CB1 receptor orthosteric ligand pocket aided by multiple polar and hydrophobic interactions with critical amino acids. In conclusion, the Aspergillus neoniveus-derived prenylated indole alkaloid acetylaszonalenin has promising anticancer activity and is amenable to further hit-to-lead optimization for the control of prostate malignancies via modulating CB1 receptor