Journals
2025 EN
Odunitan Tope T. · Apanisile Boluwatife T. · Afolabi Justinah A.
+8 more
Abstract In the fight against pathogenic infections, antimicrobial peptides (AMPs) constitute a novel and promising class of compounds that defies accepted drug development conventions like Lipinski's rule. AMPs are remarkably effective against a variety of pathogens, including viruses, bacteria, parasites, and fungi. Their effectiveness, despite differing from traditional drug‐like properties defies accepted standards. This review investigates the complex world of AMPs with an emphasis on their structural and physicochemical properties, which include size, sequence, structure, charge, and half‐life. These distinguishing characteristics set AMPs apart from conventional therapeutics that adhere to Lipinski's rules and greatly contribute to their selective targeting, reduction of resistance, multifunctionality, and broad‐spectrum efficacy. In contrast to traditional drugs that follow Lipinski's guidelines, AMPs have special qualities that play a big role in their ability to target specific targets, lower resistance, and work across a wide range of conditions. Our work is unique because of this nuanced investigation, which offers a new viewpoint on the potential of AMPs in tackling the worldwide problem of antibiotic resistance. In the face of the escalating global challenge of antibiotic resistance, antimicrobial peptides (AMPs) are innovative antimicrobial agents with unique mechanisms of action that challenge traditional Lipinski's Rule. They can withstand various microbial threats through membrane disruption, intracellular targeting, and immunomodulation. AMP versatility sets them apart from other antibiotics and their potential to address microbial infections and antibiotic resistance is growing. To fully unlock their potential, traditional drug development approaches need to be reconsidered. AMPs have revolutionary potential, paving the way for innovative solutions to health issues and transforming the antimicrobial therapy landscape.
Journals
2025 EN
Hegazi Nesrine M. · El Shabrawy Mona · Aboulthana Wael M.
+3 more
Abstract Various members of the family Brassicaceae are economically important and traditionally used to treat many disorders. Among the family members, Enarthrocarpus strangulatus Boissier is a common Egyptian species that was rarely studied. Consequently, the current study aims to characterize its phytochemical composition and assess its potential bioactivity comprehensively. A metabolomics approach integrating UPLC‐HRMS/MS‐based molecular networking enabled the dereplication of 91 metabolites, including primary ( i. e . organic acids, amino acids, fatty acids, and phospholipids) and secondary metabolites ( i. e . glucosinolates, phenolic acids, and flavonoids). Among the 91 annotated features, 13 major metabolites were fully characterized following their isolation and purification. Exclusive of only three flavonoids, all the detected metabolites are described for the first time within this species. Furthermore, the crude extract and four major isolated flavonoids were subjected to in vitro biological screening, including antioxidant, radical scavenging, anti‐diabetic, anti‐Alzheimer's, and anti‐inflammatory activities. It was noticed that nobiletin ( 61 ) exhibited the highest antioxidant and anti‐Alzheimer's activities. At the same time, isorhamnetin 3‐ O ‐glucose ( 51 ) showed the highest anti‐diabetic activity compared to the other isolated flavonoids and the total extract itself. Regarding the anti‐inflammatory activity, no obvious differences were detected numerically among all studied flavonoids.
Journals
2025 EN
Belmehdi Omar · Mssillou Ibrahim · Khalid Asaad
+7 more
Abstract Bioactive phytochemicals act as important factors with preventive and therapeutic potential in the pathogenesis of several disorders, often related to oxidative stress. Many dietary plant secondary metabolites could lower these conditions. Sorbifolin is one of these metabolites. This work is the first review of sorbifolin, a flavone detected in various plant matrices as a major compound. The present study discussed the natural sources, extraction, purification, quantification, and assessment of the biological activities of sorbifolin. Several databases including Google Scholar, Web of Sciences, and Science‐Direct were consulted for relevant English articles related to sorbifolin, the phytochemical profiles of several medicinal plants containing this compound, and its biological activities, such as antioxidant, anticancer, antimicrobial, anti‐inflammatory, and antidiabetic. The positive in vitro and in silico outcomes reported in the literature should be followed by additional in vivo and clinical investigations to further research the mechanisms of action, pharmacokinetic/pharmacodynamic activities, toxicological effects, pharmacological properties, and therapeutic potential of sorbifolin.
Journals
2025 EN
Bassam Samar M. · Abdelwahab Ibrahim A. · Teleb Mohamed
+1 more
ABSTRACT Recent episodes of viral pandemics have led to a quest for new drugs to act on emerging targets. Most challenging viruses are only mutants of already known viruses. Here comes the role of metabolomics in investigating natural secondary metabolites as sustainable antiviral drug candidates. Resins are natural plant products having the advantage of being concentrated and consisting of precious terpenoids, phenolics, and flavonoids, known for their anti‐pathogen activity. This study aimed at investigation of the major phytoconstituents in the Eucalyptus maculata (EM) resin using high resolution liquid chromatography–mass spectrometry (LC–MS/MS) and investigating its antiviral potential. In vitro screening of the standardized EM antiviral activity was performed. High resolution LC–MS/MS analysis was done for the extract followed by investigation of the possible active metabolites through molecular docking techniques against two viral protein targets; herpes simplex virus glycoprotein D (HSV gD) and B‐ and T‐lymphocyte attenuator/herpes virus entry mediator complex. The evaluation in negative and positive modes identified 29 substances and revealed the prevalence of coumaryl and galloyl derivatives, in addition to kaempferol and aromadendrin derivatives. Antiviral in vitro screening led to the conclusion of the promising effect of the resin against HSV that was further confirmed through molecular docking. EM resin represents a future sustainable drug discovery and should be further investigated as an antiviral agent.
Journals
2025 EN
Alruhaimi Reem S. · Hussein Omnia E · Alnasser Sulaiman M.
+5 more
Abstract Haloxylon salicornicum is traditionally used for the treatment of several disorders associated with inflammation. Despite it is a defense response against tissue injury and infections, inflammation can become a chronic condition that can negatively impact the body. This study investigated the effect of H. salicornicum phytochemicals nuclear factor‐kappaB (NF‐κB), inducible nitric oxide synthase (iNOS) and cytokines release by lipopolysaccharide (LPS)‐challenged macrophages in vitro . The binding affinity of the tested phytochemical towards NF‐κB and iNOS was investigated using molecular docking. Ten compounds (four coumarins, three sterols and three flavonoids) were isolated from the ethanolic extract of H. salicornicum . Treatment of LPS‐challenged macrophages with the compounds resulted in remarkable decrease in NF‐κB p65 and iNOS mRNA abundance. All compounds suppressed the production of nitric oxide (NO) and the pro‐inflammatory cytokines (tumor necrosis factor (TNF)‐α and interleukin (IL)‐6) from macrophages challenged with LPS. Molecular docking revealed the ability of the isolated phytochemicals to bind NF‐κB p65 and iNOS. In conclusion, H. salicornicum is a rich source of phytochemicals with anti‐inflammatory properties. The anti‐inflammatory efficacy of H. salicornicum phytoconstituents is mediated via their ability to modulate NF‐κB and iNOS, and suppress the release of NO, TNF‐α, and IL‐6 from macrophages.
Journals
2025 EN
Abdallah Abdallah E. · Eissa Ibrahim H. · Mehany Ahmed B. M.
+5 more
Abstract New thalidomide analogs have been designed and synthesized by hybridizing the immunomodulatory gutarimide moiety with three antiproliferative nuclei: quinazolinedione, phthalazinedione, and quinoxalinone. The biological results revealed the strong impact of quinazoline derivatives 7 a and 28 , and phthalazine based 20 a against HepG‐2, MCF‐7, PC3, and HCT‐116 cell lines, compared to thalidomide. In particular, compound 20 a was the most promising as it had far better biological activity than thalidomide with regard to inhibition of TNF‐ α , IL‐6, caspase 3, COX‐I/II, and VEGFR‐2, as well as cell cycle arrest, and apoptosis rate enhancement in MCF‐7 cells, the most sensitive cell line to the current new molecules. Compound 20 a caused reduction in levels of TNF‐ α and IL‐6 by 75.22 % and 82.51 %, respectively. It elevated the caspase‐3 level by 7.21‐fold. Furthermore, IC 50 against COX‐I, COX‐II, and VEGFR‐2 were 0.65 μM, 0.33 μM, and 232 nM, respectively. In addition, it raised the apoptosis rate from 65.65 % to 99.89 %. Moreover, 20 a was further examined through a docking study and a 200 ns molecular dynamics simulation for its complex with VEGFR‐2, along with computational ADME properties. This work suggests the high significance of compounds 20 a , 7 a and 28 , as lead compounds for development of new effective immunomodulatory antitumor drugs.
Journals
2025 EN
Shakoor Abdul · Jan Faheem · Rahman Sudais
+10 more
Abstract In this study, eleven hydrazone‐Schiff bases bearing benzimidazole moiety were synthesized successfully via three step reactions and structures of these products were deduced by HR‐ESI‐MS, 1 H‐, and 13 C‐NMR spectroscopic techniques. Lastly, these derivatives were tested for their in vitro urease inhibitory potential. Six compounds among the series attributed excellent inhibition with IC 50 values of 7.20±0.59 to 19.61±1.10 μM better than the reference drug thiourea (IC 50 =22.12±1.20 μM). Similarly, three derivatives showed significant while two compounds showed less inhibitory effects against the urease enzyme. The molecular docking analysis was carried out to reveal the binding modes and types of interaction taking place between protein (urease) and synthesized compounds. The Density Functional Theory (DFT) calculations were performed at B3LYP/6‐311++G(d,p) to check the structure stability. For the account of intramolecular interaction, the DFT−D3 and Reduced Density Gradient (RDG) analysis were performed. Furthermore, the chemical nature of all compounds was explored by TD‐DFT method using CAM−B3LYP functional with 6–311++G(d,p) basis set. The dynamic simulation as well as MMGBSA studies validated the binding affinity and stability of the ligand receptor complex, displaying main interactions contributing in the biological activity of the product derivatives.
Journals
2025 EN
Alharbi Osama · AlMutairi Khalid Awadh · Ibrahim Munjed M.
+2 more
ABSTRACT In the current study, new pyranopyrazole analogs ( 9a–d and 10a–d ) were synthesized through a one‐pot condensation reaction of 2‐arylacetohydrazide. The inhibitory abilities were investigated against the xanthine oxidase (XO) enzyme through experimental and molecular docking analyses. The synthesis studies were based on ultrasound‐mediated condensation reactions of four‐component containing 2‐arylacetohydrazide, ethyl acetoacetate, indoline‐2,3‐dione, and ethyl 2‐cyanoacetate/malononitrile in various solvents and catalysts to yield pyranopyrazole analogs ( 9a–d and 10a–d ) in a short reaction time and remarkably favorable yields ranging from 79% to 92%. On the basis of the XO inhibition study of compounds 9a–d and 10a–d , compound 10d was the most potent (IC 50 = 0.09 ± 0.22 µM), followed by 9c (0.12 ± 0.11 µM). With IC 50 values of 0.20 ± 0.27 and 0.17 ± 0.11 µM respectively, compounds 10a and 10c exhibited moderate activity. The other compounds have shown less activity compared to the allopurinol control (IC 50 = 0.14 ± 0.10 µM). Furthermore, in the molecular docking analysis, compound 10d was predicted to have the highest binding affinity against the target XO enzyme.
Journals
2025 EN
ElShiekh Riham A. · Atwa Ahmed M. · Elgindy Ali M.
+4 more
ABSTRACT α‐Hederin, a naturally occurring compound found in various plant sources, has remarkable properties and therapeutic potential for human health. One notable attribute is its potent anti‐inflammatory activity, such as in arthritis, asthma, and inflammatory bowel disease. In addition, it exhibits notable antioxidant effects implicated in the development of chronic diseases, including cardiovascular disorders and certain types of cancer. According to research, it may limit the growth and proliferation of cancer cells, making it a possible candidate for future cancer treatments. Moreover, it is a promising neuroprotective agent and enhances cognitive function, suggesting its potential in the treatment of neurodegenerative illnesses like Alzheimer's and Parkinson's disease. The multifaceted benefits of α‐hederin make it an intriguing compound with significant therapeutic implications. As research progresses, exploring its mechanisms of action and clinical applications is warranted. Harnessing the potential of α‐hederin may pave the way for innovative treatment strategies and improved outcomes in the battle against various chronic diseases.
Journals
2025 EN
Yusuf Amina J. · Ibrahim Nasir · Abdullahi Musa I.
+2 more
Abstract Snakebite envenomation remains a significant medical challenge, particularly in tropical and subtropical regions. The present study investigates the inhibitory potential of Zingiber officinale (ginger) and its bioactive compounds against Naja nigricollis venom using in silico approaches and animal models. No protection was observed in the in vivo studies but the extract of the plant was able to prolong the time of death with mean survival time ranging from 2.01–2.83 hours. In terms of the in vitro studies, the extract was able to significantly ( p<0.05 ) detoxify the N. nigricollis venom by 80 % at the graded doses; standard antisnake venom (ASV) offered 100 % protection to mice. Molecular docking analysis revealed strong binding affinities between the bioactive compounds and the PLA 2 enzyme, indicating potential inhibitory effects. The stability and dynamics of the protein‐ligand complexes were further validated through molecular dynamics (MD) simulations, which confirmed the persistence of these interactions over time. In conclusion, the findings suggest that the bioactive compounds from Z. officinale could serve as promising inhibitors of PLA 2 , providing a foundation for the development of novel snakebite envenomation therapies.