Correction: Reinvestigation of Passerini and Ugi scaffolds as multistep apoptotic inducers dual modulation of caspase 3/7 and P53-MDM2 signaling for halting breast cancer.

[This corrects the article DOI: 10.1039/D3RA04029A.].

Preparation and kinetic studies of a new antibacterial sodium alginate gelatin hydrogel composite.

This study involved synthesis of a novel antibacterial heterocyclic compound, sodium 2-(2-(3-phenyl-1, 2, 4-oxadiazol-5-yl) phenoxy) acetate abbreviated as Na-POPA. Further development of a biocompatible, pH-responsive hydrogel drug carrier prepared utilizing the natural polymers gelatin and sodium alginate. The compound loaded on the hydrogel represented new drug delivery system.

Zwitterionic MOF-embedded alginate beads with polydopamine surface functionalization for efficient doxycycline removal: Optimization and mechanistic study.

The adsorptive removal of amphoteric antibiotics like doxycycline (DOX) is a difficult task because of the electrostatic repulsion between these amphoteric molecules and adsorbents. For this purpose, a zwitter adsorbent was fabricated by incorporating zwitter ZIF-67/MIL-88A binary MOF into the matrix of alginate (Alg); in addition, the surface of the beads was modified by polydopamine (PDA). The batch experiments implied the super-high adsorption efficacy of ZIF-67/MIL-88A@Alg@PDA toward DOX attained 384.

Zein-based nisin-loaded electrospun nanofibers as active packaging mats for control of Listeria monocytogenes on peach.

Zein-based nanofibers (NFs) functionalized with nisin (NS), reinforced with montmorillonite nanoclay (nMMT) were fabricated by uniaxial electrospinning (ES) for the first time to preserve yellow peach. Spinnability/viscosity/conductivity optimizations generated porous (95.09%), bead-free, ultrathin (119 nm) NFs of low hydrophobicity (26.

New 1,2,4-oxadiazole derivatives as potential multifunctional agents for the treatment of Alzheimer's disease: design, synthesis, and biological evaluation.

A series of new 1,2,4-oxadiazole-based derivatives were synthesized and evaluated for their anti-AD potential. The results revealed that eleven compounds (1b, 2a-c, 3b, 4a-c, and 5a-c) exhibited excellent inhibitory potential against AChE, with IC values ranging from 0.00098 to 0.

Design, synthesis, and biological evaluation of 1,2,4-oxadiazole-based derivatives as multitarget anti-Alzheimer agents.

A series of novel 1,2,4-oxadiazole-based derivatives were synthesized and evaluated for their potential anti-Alzheimer disease activity. The results revealed that compounds 2b, 2c, 2d, 3a, 4a, 6, 9a, 9b, and 13b showed excellent inhibitory activity against acetylcholinesterase (AChE) with IC values in the range of 0.0158 to 0.

Design and Synthesis of Quinoxaline Hybrids as Modulators of HIF-1a, VEGF, and p21 for Halting Colorectal Cancer.

A library of 16 3-benzyl- -substituted quinoxalin-2-ones was synthesized as -substituted quinoxalines and quinoxaline-triazole hybrids via click reaction. These compounds were tested for their anticancer activity via MTT assay on HCT-116 and normal colonocyte cell lines to assess their cytotoxic potentials and safety profiles. Overall, compounds , , , and were found to be promising anticolorectal cancer agents; they exhibited remarkable cytotoxicity (IC 0.

Correction: Targeting EGFR/PI3K/AKT/mTOR signaling in lung and colon cancers: synthesis, antitumor evaluation of new 1,2,4-oxdiazoles tethered 1,2,3-triazoles.

[This corrects the article DOI: 10.1039/D4RA02222J.].

Targeting EGFR/PI3K/AKT/mTOR signaling in lung and colon cancers: synthesis, antitumor evaluation of new 1,2,4-oxdiazoles tethered 1,2,3-triazoles.

The EGFR/PI3K/Akt/mTOR pathway is important for metastasis, medication resistance, apoptosis prevention, and malignant transformation. Mutations in lung and colon cancer typically change this pathway's expression. As a result, a novel class of 1,2,4-oxdiazoles that are attached to 1,2,3-triazoles, 5-11, were created as possible anticancer drugs.

Novel sulfonamide derivatives as multitarget antidiabetic agents: design, synthesis, and biological evaluation.

A series of new sulfonamide derivatives connected through an imine linker to five or seven membered heterocycles were designed and synthesized. All synthesized derivatives were characterized using a variety of spectroscopic methods, including IR, HNMR, and CNMR. α-glucosidase and α-amylase inhibition activities, as well as glucose uptake were assessed for each of the synthesized compounds.

Challenging the anticolorectal cancer capacity of quinoxaline-based scaffold via triazole ligation unveiled new efficient dual VEGFR-2/MAO-B inhibitors.

Monoamine oxidases (MAOs) and vascular endothelial growth factor receptor-2 (VEGFR-2) are promoters of colorectal cancer (CRC) and central signaling nodes in epithelial-mesenchymal transition (EMT) induced by activating hypoxia-inducible factors (HIFs). Herein, a novel series of rationally designed triazole-tethered quinoxalines were synthesized and evaluated against HCT-116 CRC cells. The tailored scaffolds combine the pharmacophoric themes of both VEGFR-2 inhibitors and MAO inhibitors.

Reinvestigation of Passerini and Ugi scaffolds as multistep apoptotic inducers dual modulation of caspase 3/7 and P53-MDM2 signaling for halting breast cancer.

Selective induction of breast cancer apoptosis is viewed as the mainstay of various ongoing oncology drug discovery programs. Passerini scaffolds have been recently exploited as selective apoptosis inducers a caspase 3/7 dependent pathway. Herein, the optimized Passerini caspase activators were manipulated to synergistically induce P53-dependent apoptosis modulating the closely related P53-MDM2 signaling axis.

Repurposing 1,2,4-oxadiazoles as SARS-CoV-2 PLpro inhibitors and investigation of their possible viral entry blockade potential.

Although vaccines are obviously mitigating the COVID-19 pandemic diffusion, efficient complementary antiviral agents are urgently needed to combat SARS-CoV-2. The viral papain-like protease (PLpro) is a promising therapeutic target being one of only two essential proteases crucial for viral replication. Nevertheless, it dysregulates the host immune sensing response.

4-(-Phthalimido)phenyl Isonitrile as a Novel Convertible Isocyanide Analogue with the Odorless Property as an Extra Bonus.

We explored a new isonitrile, namely 4-(-phthalimido)phenyl isonitrile, with extraordinary features. The novel isocyanide has a pharmacophore, the phthalimido (Pht) group, that possesses promising pharmaceutical activities. We found that the novel isonitrile is unexpectedly odorless as an extra bonus which makes its handling easy in organic synthesis to serve as a scaffold for building several new amide derivatives through multicomponent reactions, overcoming the stink of common aromatic isonitriles such as phenyl isonitrile, benzyl isonitrile, -nitrophenyl isonitrile, and ethyl 4-isocyano benzoate.

Structure optimization of new tumor-selective Passerini α-acyloxy carboxamides as Caspase-3/7 activators.

Selective elimination of tumors has always been the mainstay of oncology research. The on-going research underlying the cellular apoptotic mechanisms reveal caspases activation, especially the key effector caspase-3, as a personalized tumor-selective therapeutic strategy. Our continued research protocol has exploited new optimized Passerini α-acyloxy carboxamides as efficient apoptotic inducers via caspase-3/7 dependent mechanism with highly selective anticancer profiles.

Review on fluorinated nucleoside/non-nucleoside FDA-approved antiviral drugs.

FDA-approved antiviral agents represent an important class that has attracted attention in recent years to combat current and future threats of viral pandemics. Fluorine ameliorates the electronic, lipophilic and steric problems of drugs. Additionally, fluorine can prolong drug activity and improve metabolic stability, thereby, modifying their pharmacodynamic and pharmacokinetic character.

Nature-inspired new isoindole-based Passerini adducts as efficient tumor-selective apoptotic inducers via caspase-3/7 activation.

The development of novel therapeutics promoting selective tumor elimination is the mainstay of clinical oncology. Emerging insights into tumor targeting reveal caspases activation, especially caspase-3, as a personalized anticancer strategy. Our on-going cancer research has exploited Passerini α-acyloxy carboxamides as caspase-3/7-dependent apoptotic inducers.

Synthesis of a new magnetic Sulfacetamide-Ethylacetoacetate hydrazone-chitosan Schiff-base for Cr(VI) removal.

In this study, a novel magnetic organic-inorganic composite was fabricated. Chitosan, sulfacetamide and ethylacetoacetae were used to prepare a new Sulfacetamide-Ethylacetoacetate hydrazone-chitosan Schiff-base (SEH-CSB) with a variety of active sites that capable of forming coordinate covalent bonds with Cr(VI). This was followed by modification of the formed SHE-CSB with NiFeO to obtain the magnetic Chitosan-Schiff-base composite (NiFeO@SEH-CSB).

Exploration of Nitroaromatic Antibiotics Sanger's Reagent: Synthesis, , and Antimicrobial Evaluation.

Facile synthesis of molecular hybrids containing a 2,4-dinitrophenyl moiety was achieved nucleophilic aromatic substitution of the fluoride anion of Sanger's reagent (2,4-dinitrofluorobenzene) with various , , and nucleophiles, considered as bioactive moieties. Antimicrobial evaluation of the new hybrids was carried out using amoxicillin and nystatin as antibacterial and antifungal reference standards, respectively. MIC test results identified the compounds , and as the most active hybrids against standard strains and multidrug-resistant strains (MDR) of , , and .

Halting colorectal cancer metastasis via novel dual nanomolar MMP-9/MAO-A quinoxaline-based inhibitors; design, synthesis, and evaluation.

Matrix metalloproteinase-9 (MMP-9) and monoamine oxidase-A (MAO-A) are central signaling nodes in CRC and promotors of distant metastasis associated with high mortality rates. Novel series of quinoxaline-based dual MMP-9/MAO-A inhibitors were synthesized to suppress CRC progression. The design rationale combines the thematic pharmacophoric features of MMP-9 and MAO-A inhibitors in hybrid scaffolds.

Beyond direct Nrf2 activation; reinvestigating 1,2,4-oxadiazole scaffold as a master key unlocking the antioxidant cellular machinery for cancer therapy.

Harnessing the antioxidant cellular machinery has sparked considerable interest as an efficient anticancer strategy. Activating Nrf2, the master switch of the cellular redox system, suppresses ROS, alleviates oxidative stress, and halts cancer progression. 1,2,4-oxadiazoles are iconic direct Nrf2 activators that disrupt Nrf2 interaction with its endogenous repressor Keap1.

Two decades of recent advances of Ugi reactions: synthetic and pharmaceutical applications.

Multicomponent reactions (MCRs) are powerful synthetic tools in which more than two starting materials couple with each other to form multi-functionalized compounds in a one-pot process, the so-called "tandem", "domino" or "cascade" reaction, or utilizing an additional step without changing the solvent, the so-called a sequential-addition procedure, to limit the number of synthetic steps, while increasing the complexity and the molecular diversity, which are highly step-economical reactions. The Ugi reaction, one of the most common multicomponent reactions, has recently fascinated chemists with the high diversity brought by its four- or three-component-based isonitrile. The Ugi reaction has been introduced in organic synthesis as a novel, efficient and useful tool for the preparation of libraries of multifunctional peptides, natural products, and heterocyclic compounds with stereochemistry control.

Fluorinated phenylalanines: synthesis and pharmaceutical applications.

Recent advances in the chemistry of peptides containing fluorinated phenylalanines (Phe) represents a hot topic in drug research over the last few decades. ᴅ- or ʟ-fluorinated phenylalanines have had considerable industrial and pharmaceutical applications and they have been expanded also to play an important role as potential enzyme inhibitors as well as therapeutic agents and topography imaging of tumor ecosystems using PET. Incorporation of fluorinated aromatic amino acids into proteins increases their catabolic stability especially in therapeutic proteins and peptide-based vaccines.

Battle tactics against MMP-9; discovery of novel non-hydroxamate MMP-9 inhibitors endowed with PI3K/AKT signaling attenuation and caspase 3/7 activation via Ugi bis-amide synthesis.

Matrix metalloproteinases (MMPs) are major modulators of the tumor microenvironment. They participate in extracellular matrix turnover, tumor growth, angiogenesis and metastasis. Accordingly, MMPs inhibition seems to be ideal solution to control cancer.

Metabolism and hydrophilicity of the polarised 'Janus face' all- tetrafluorocyclohexyl ring, a candidate motif for drug discovery.

The metabolism and polarity of the all- tetra-fluorocyclohexane motif is explored in the context of its potential as a motif for inclusion in drug discovery programmes. Biotransformations of phenyl all- tetra-, tri- and di- fluoro cyclohexanes with the human metabolism model organism illustrates various hydroxylated products, but limited to benzylic hydroxylation for the phenyl all- tetrafluorocyclohexyl ring system. Evaluation of the lipophilicities (log ) indicates a significant and progressive increase in polarity with increasing fluorination on the cyclohexane ring system.