Efficient Microwave-Assisted Solvent-Free Synthesis and Molecular Docking Studies of 2-pyridone derivatives as Anticancer Agents and Evaluation of Cytotoxic Effects

Introduction: A green protocol will be used to synthesize a novel series of 3-cyano-5- arylazo-pyridones (9a-c) and (10d-i). Methodology: Structures of the new products will be confirmed on the basis of spectroscopic data (FT-IR, 1D, NMR) as well as alternative synthetic routes, anticancer cell-line will be investigated and also molecular docking studies will be applied. Results: The activity against different cancer cell-line will be studied. Compounds with electron withdrawal group showed the highest activities

An Insight into All Tested Small Molecules against Fusarium oxysporum f. sp. Albedinis : A Comparative Review

Bayoud disease affects date palms in North Africa and the Middle East, and many researchers have used various methods to fight it. One of those methods is the chemical use of synthetic compounds, which raises questions centred around the compounds and common features used to prepare targeted molecules. In this review, 100 compounds of tested small molecules, collected from 2002 to 2022 in Web of Sciences, were divided into ten different classes against the main cause of Bayoud disease pathogen Fusarium oxysporum f. sp. albedinis (F.o.a.) with structure-activity relationship (SAR) interpretations for pharmacophore site predictions as (delta(-)center dot center dot center dot delta(-)), where 12 compounds are the most efficient (one compound from each group). The compounds, i.e., (Z)-1-(1.5-Dimethyl-1H-pyrazole-3-yl)-3-hydroxy but-2-en-1-one 7, (Z)-3-(phenyl)-1-(1,5-dimethyl-1H-pyrazole-3-yl)-3-hydroxyprop-2-en-1-one 23, (Z)-1-(1,5-Dimethyl-1H-pyrazole-3-yl)-3-hydroxy-3-(pyridine-2-yl)prop-2-en-1-one 29, and 2,3-bis-[(2-hydroxy-2-phenyl)ethenyl]-6-nitro-quinoxaline 61, have antifungal pharmacophore sites (delta(-)center dot center dot center dot delta(-)) in common in N1---O4, whereas other compounds have only one delta(-) pharmacophore site pushed by the donor effect of the substituents on the phenyl rings. This specificity interferes in the biological activity against F.o.a. Further understanding of mechanistic drug-target interactions on this subject is currently underway.Peer reviewe

Current perspectives in the discovery of newer medications against the outbreak of Covid-19

A rapid and increasing spread of COVID-19 pandemic disease has been perceived worldwide in 2020. The current COVID-19 disease outbreak is due to the spread of SARS-CoV-2. SARS-CoV-2 is a new strain of coronavirus that has spike protein on the envelope. The spike protein of the virus binds with the ACE-2 receptor of the human lungs surface for entering into the host. Therefore, the blocking of viral entry into the host by targeting the spike protein has been suggested to be a valid strategy to treat COVID-19. The patients of COVID-19 were found to be asymptomatic, cold, mild to severe respiratory illness, and leading to death. The severe illness has been noted mainly in old age people, cardiovascular disease patients, and respiratory disease patients. However, the long-term health effects due to COVID-19 are not yet known. Recently, the vaccines were authorized to protect from COVID-19

An Insight into All Tested Small Molecules against Fusarium oxysporum f. sp. Albedinis: A Comparative Review

Bayoud disease affects date palms in North Africa and the Middle East, and many researchers have used various methods to fight it. One of those methods is the chemical use of synthetic compounds, which raises questions centred around the compounds and common features used to prepare targeted molecules. In this review, 100 compounds of tested small molecules, collected from 2002 to 2022 in Web of Sciences, were divided into ten different classes against the main cause of Bayoud disease pathogen Fusarium oxysporum f. sp. albedinis (F.o.a.) with structure–activity relationship (SAR) interpretations for pharmacophore site predictions as (δ−···δ−), where 12 compounds are the most efficient (one compound from each group). The compounds, i.e., (Z)-1-(1.5-Dimethyl-1H-pyrazole-3-yl)-3-hydroxy but-2-en-1-one 7, (Z)-3-(phenyl)-1-(1,5-dimethyl-1H-pyrazole-3-yl)-3-hydroxyprop-2-en-1-one 23, (Z)-1-(1,5-Dimethyl-1H-pyrazole-3-yl)-3-hydroxy-3-(pyridine-2-yl)prop-2-en-1-one 29, and 2,3-bis-[(2-hydroxy-2-phenyl)ethenyl]-6-nitro-quinoxaline 61, have antifungal pharmacophore sites (δ−···δ−) in common in N1---O4, whereas other compounds have only one δ− pharmacophore site pushed by the donor effect of the substituents on the phenyl rings. This specificity interferes in the biological activity against F.o.a. Further understanding of mechanistic drug–target interactions on this subject is currently underway

An Insight into All Tested Small Molecules against Fusarium oxysporum f. sp. Albedinis: A Comparative Review

Bayoud disease affects date palms in North Africa and the Middle East, and many researchers have used various methods to fight it. One of those methods is the chemical use of synthetic compounds, which raises questions centred around the compounds and common features used to prepare targeted molecules. In this review, 100 compounds of tested small molecules, collected from 2002 to 2022 in Web of Sciences, were divided into ten different classes against the main cause of Bayoud disease pathogen Fusarium oxysporum f. sp. albedinis (F.o.a.) with structure–activity relationship (SAR) interpretations for pharmacophore site predictions as (δ−···δ−), where 12 compounds are the most efficient (one compound from each group). The compounds, i.e., (Z)-1-(1.5-Dimethyl-1H-pyrazole-3-yl)-3-hydroxy but-2-en-1-one 7, (Z)-3-(phenyl)-1-(1,5-dimethyl-1H-pyrazole-3-yl)-3-hydroxyprop-2-en-1-one 23, (Z)-1-(1,5-Dimethyl-1H-pyrazole-3-yl)-3-hydroxy-3-(pyridine-2-yl)prop-2-en-1-one 29, and 2,3-bis-[(2-hydroxy-2-phenyl)ethenyl]-6-nitro-quinoxaline 61, have antifungal pharmacophore sites (δ−···δ−) in common in N1---O4, whereas other compounds have only one δ− pharmacophore site pushed by the donor effect of the substituents on the phenyl rings. This specificity interferes in the biological activity against F.o.a. Further understanding of mechanistic drug–target interactions on this subject is currently underway

New N-Alkylated Heterocyclic Compounds as Prospective NDM1 Inhibitors : Investigation of In Vitro and In Silico Properties

A new family of pyrazole-based compounds (1-15) was synthesized and characterized using different physicochemical analyses, such as FTIR, UV-Visible, H-1, C-13 NMR, and ESI/LC-MS. The compounds were evaluated for their in vitro antifungal and antibacterial activities against several fungal and bacterial strains. The results indicate that some compounds showed excellent antibacterial activity against E. coli, S. aureus, C. freundii, and L. monocytogenes strains. In contrast, none of the compounds had antifungal activity. Molecular electrostatic potential (MEP) map analyses and inductive and mesomeric effect studies were performed to study the relationship between the chemical structure of our compounds and the biological activity. In addition, molecular docking and virtual screening studies were carried out to rationalize the antibacterial findings to characterize the modes of binding of the most active compounds to the active pockets of NDM1 proteins.Peer reviewe

DNA-binding and anticancer activity of binuclear gold(I) alkynyl complexes with a phenanthrenyl bridging ligand

3,6-Diethynyl-9,10-diethoxyphenanthrene (4) was synthesized from phenanthrene and employed in the synthesis of the binuclear gold(I) alkynyl complexes (R3P)Au(C≡C-3-[C14H6-9,10-diethoxy]-6-C≡C)Au(PR3) (R = Ph (5a), Cy (5b)). The diyne 4 and complexes 5a and 5b were characterized by NMR spectroscopy, mass spectrometry, and elemental analysis. UV-Vis spectroscopy studies of the metal complexes and precursor diyne show strong π → π* transitions in the near UV region that red shift by ca. 50 nm upon coordination at the gold centers. The emission spectrum of 4 shows an intense fluorescence band centered at 420 nm which red shifts, slightly upon coordination of 4 to gold. Binding studies of 4, 5a, and 5b against calf thymus DNA were carried out, revealing that 4, 5a, and 5b have ≥40% stronger binding affinities than the commonly used intercalating agent ethidium bromide. The molecular docking scores of 4, 5a, and 5b with B-DNA suggest a similar trend in behavior to that observed in the DNA-binding study. Unlike the ligand 4, promising anticancer properties for 5a and 5b were observed against several cell lines; the DNA binding capability of the precursor alkyne was maintained, and its anticancer efficacy enhanced by the gold centers. Such phenanthrenyl complexes could be promising candidates in certain biological applications because the two components (phenanthrenyl bridge and metal centers) can be altered independently to improve the targeting of the complex, as well as the biological and physicochemical properties.This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, Saudi Arabia under grant no. (KEP-44-130-40). The authors, therefore, acknowledge with thanks DSR technical and financial support

Corrigendum: Synthesis and cytotoxic activity of novel indole derivatives and their in silico screening on spike glycoprotein of sars-cov-2

The authors Kaliappillai Vijayakumar, Magda H. Abdellattif, Mohd Shahbaaz were not included in the published article and the authors Daoud Ali, Saud Alarifi, and Amal Alotaibi were mistakenly included in the author list. The author list has been corrected throughout the article and in the Author Contributions statement. In addition, the funding information was incorrect and has been amended to include funding for Magda H. Abdellattif. The corrected Author Contributions, Funding and Acknowledgments statements appears below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated

Computational approaches for the design of novel anticancer compounds based on pyrazolo[3,4-d]pyrimidine derivatives as trap1 inhibitor

In the present in-silico study, various computational techniques were applied to determine potent compounds against TRAP1 kinase. The pharmacophore hypothesis DHHRR_1 consists of important features required for activity. The 3D QSAR study showed a statistically significant model with R2 = 0.96 and Q2 = 0.57. Leave one out (LOO) cross-validation (R2 CV = 0.58) was used to validate the QSAR model. The molecular docking study showed maximum XP docking scores (−11.265, −10.532, −10.422, −10.827, −10.753 kcal/mol) for potent pyrazole analogs (42, 46, 49, 56, 43), respectively, with significant interactions with amino acid residues (ASP 594, CYS 532, PHE 583, SER 536) against TRAP1 kinase receptors (PDB ID: 5Y3N). Furthermore, the docking results were validated using the 100 ns MD simulations performed for the selected five docked complexes. The selected inhibitors showed relatively higher binding affinities than the TRAP1 inhibitor molecules present in the literature. The ZINC database was used for a virtual screening study that screened ZINC05297837, ZINC05434822, and ZINC72286418, which showed similar binding interactions to those shown by potent ligands. Absorption, distribution, metabolism, and excretion (ADME) analysis showed noticeable results. The results of the study may be helpful for the further development of potent TRAP1 inhibitors

Folecitin isolated from hypericum oblongifolium exerts neuroprotection against lipopolysaccharide-induced neuronal synapse and memory dysfunction via p-AKT/Nrf-2/HO-1 signalling pathway

Neurodegenerative diseases, especially Alzheimer's disease (AD), are characterised with neuronal synapse and memory dysfunction, and thus, there is an urgent need to find novel therapeutic medicines that can target different pathways to restore the deficits. In this investigation, we assessed the medicinal potency of folecitin (a flavonoid isolated from Hypericum oblongifolium Wall.) against lipopolysaccharide (LPS)-induced amyloidogenic amyloid beta (Aβ) production pathway-mediated memory impairment in mice. The LPS was administered intraperitonially (i.p.) 250 μg/kg/day for 3 consecutive weeks, followed by the coadministration of folecitin (30 mg/kg/day) with LPS for the last two weeks (2nd and 3rd week). The expression of various proteins involved in synapse, neuronal death, and Aβ generation was evaluated using the Western blot approach. Results indicated that folecitin significantly decreased LPS-induced apoptotic proteins; expressed BAX, PARP-1, and caspase-3 proteins; and inhibited BACE1 that cleaves transmembrane amyloid precursor protein and the amyloidogenic Aβ production pathway. Folecitin restored both preneural and postneuronal synapse, accompanied by the improvement in memory impairment. Moreover, folecitin significantly activated endogenous antioxidant proteins Nrf-2 and HO-1 by stimulating the phosphorylation of Akt proteins. These findings indicate that folecitin might be a promising target for developing novel medication to treat neurodegenerative disorders caused by neurotoxins