Design, synthesis, and biological evaluation of novel 2,3-Di-O-Aryl/Alkyl sulfonate derivatives of l-ascorbic acid: Efficient access to novel anticancer agents via in vitro screening, tubulin polymerization inhibition, molecular docking study and ADME predictions.

A series of novel l-ascorbic acid derivatives bearing aryl and alkyl sulfonate substituents were synthesized and characterized. In vitro anticancer evaluation against MCF-7 (breast) and A-549 (lung) cancer cell lines revealed potent activity for most of the compounds, with 2b being equipotent to the standard drug colchicine against MCF-7 (IC = 0.04 μM).

Exploring binding potential of two new indole alkaloids from against third and fourth generation EGFR: druglikeness, ADMET, docking, DFT, molecular dynamics simulation, and MMGBSA study.

This study investigates the anti-cancer potential of recently discovered indole alkaloids from against third and fourth-generation EGFR mutations using computational tools. Through ADMET profiling, druglikeness prediction, docking, and simulations, we assessed their pharmacokinetics, binding interactions, and stability. Promising druglikeness and binding affinity were observed, particularly for (±)-19-O-butylangustoline, which demonstrated stronger binding against both EGFR mutants.

Molecular Docking, Pharmacokinetic and Molecular Simulation Analysis of Novel Mono-Carbonyl Curcumin Analogs as L858R/T790M/C797S Mutant EGFR Inhibitors.

Introduction: Curcumin, an anticancer natural compound with multiple pharmacological activities, has a weak pharmacokinetic and instability due to diketone moiety. Curcumin's stability challenges can be overcome by removing the diketone moiety and shortening the 7-carbon chain, resulting in mono-carbonyl analogs. Cancer proliferation is caused by the activation of Epidermal Growth Factor (EGFR) pathways.

A Review: Exploring Synthetic Schemes and Structure-activity Relationship (SAR) Studies of Mono-carbonyl Curcumin Analogues for Cytotoxicity Inhibitory Anticancer Activity.

Introduction: Cancer is the major cause of death globally. Cancer can be treated with naturally occurring Curcumin nuclei. Curcumin has a wide range of biological actions, including anti-inflammatory and anti-cancer properties.

Design, synthesis, and biological evaluation of novel quinoline derivatives as small molecule mutant EGFR inhibitors targeting resistance in NSCLC: In vitro screening and ADME predictions.

Here in, we report the design, synthesis and in vitro anticancer activity of a novel series of 24 quinoline analogues of substituted amide and sulphonamide derivatives. The anticancer activity of the synthesised compounds was evaluated against the HCC827, H1975 (L858R/T790 M), A549 (WT EGFR), A-549 and BEAS-2B cell lines. The majority of quinoline compounds demonstrated a significant cytotoxic effect.

Molecular dynamic simulations based discovery and development of thiazolidin-4-one derivatives as EGFR inhibitors targeting resistance in non-small cell lung cancer (NSCLC).

Targeting kinases with oncogenic driver mutations in malignancies with allosteric kinase inhibitors is a promising new treatment technique. EGFR inhibitors targeting the L858R/T790M/C797S mutation bearing thiazolidine-4-one scaffold were discovered, optimized, synthesized, and biologically evaluated. According to and studies, compounds and resulted to be highly potent with IC values of 120 nM and 134 nM and good selectivity.

Explorations of novel pyridine-pyrimidine hybrid phosphonate derivatives as aurora kinase inhibitors.

For developing novel therapeutic agents with good anticancer activities, a series of novel pyridine-pyrimidine hybrid phosphonate derivatives4(a-q) were synthesized by the Kabachnik-Fields method using CAN as catalyst. The compound 4o exhibited the most potent anticancer activity with an IC value of 13.62 μM, 17.

Free energy perturbation guided Synthesis with Biological Evaluation of Substituted Quinoline derivatives as small molecule L858R/T790M/C797S mutant EGFR inhibitors targeting resistance in Non-Small Cell Lung Cancer (NSCLC).

Two different schemes of novel substituted quinoline derivatives were designed and synthesized via simple reaction steps and conditions. A comparative molecular docking study was carried out on two different types of EGFR enzymes which include wild-type (PDB: 4I23) and T790M mutated (PDB: 2JIV) respectively. Compounds were also validated upon T790M/C797S mutated (PDB ID: 5D41) EGFR enzyme at the allosteric binding site.

Design and synthesis of novel conformationally constrained 7,12-dihydrodibenzo[b,h][1,6] naphthyridine and 7H-Chromeno[3,2-c] quinoline derivatives as topoisomerase I inhibitors: In vitro screening, molecular docking and ADME predictions.

Novel non-camptothecin (non-CPT) class of conformationally constrained, hitherto unknown 7,12-dihydrodibenzo[b,h][1,6] naphthyridine and 7H-Chromeno[3,2-c] quinoline derivatives have been designed, synthesized and evaluated for anti-cancer activity. In vitro anti-proliferation evaluation against human cancer cell lines (A549 and MCF-7) exhibited significant cytotoxicity. Among the derivatives (8-24), 8 (IC 0.

One pot synthesis, in silico study and evaluation of some novel flavonoids as potent topoisomerase II inhibitors.

A library of novel flavonoid derivatives with diverse heterocyclic groups was designed and efficiently synthesized. Structures of the newly synthesized compounds 4a-i and 8a-l have been characterized by H NMR, C NMR, MS and elemental analysis. Anticancer activities were evaluated against MCF-7, A549, HepG2 and MCF-10A by MTT based assay.

Computational and Synthetic approach with Biological Evaluation of Substituted Quinoline derivatives as small molecule L858R/T790M/C797S triple mutant EGFR inhibitors targeting resistance in Non-Small Cell Lung Cancer (NSCLC).

New substituted quinoline derivatives were designed and synthesized via a five-step modified Suzuki coupling reaction. A comparative molecular docking study was carried out on two different types of EGFR enzymes which include wild-type (PDB: 4I23) and T790M mutated (PDB: 2JIV) respectively. Compounds were also validated upon T790M/C797S mutated (PDB ID: 5D41) EGFR enzyme at the allosteric binding site.

Ultrasound assisted synthesis of tetrazole based pyrazolines and isoxazolines as potent anticancer agents via inhibition of tubulin polymerization.

In search of new active molecules against MCF-7, A549 and HepG2, tetrazole based pyrazoline and isoxazoline derivatives under both conventional and ultrasonic irradiation method were designed and efficiently synthesized. Structures of newly synthesized compounds 5a-h and 6a-h were characterized by H NMR, C NMR, MS and elemental analysis. Several derivatives were found to be excellent cytotoxic against MCF-7, A549 and HepG2 cell lines characterized by lower IC values (0.

Development of triple mutant T790M/C797S allosteric EGFR inhibitors: a computational approach.

The mutations concerned with non-small cell lung cancer involving epidermal growth factor receptor of tyrosine kinase family have primarily targeted. EGFR inhibitors binding allosterically to C797S mutant EGFR enzyme have been developed. Here, database building, library screening performing R-group enumeration and scaffold hopping technique for increasing the EGFR binding affinity of compounds have been carried out.

Synthesis and evaluation of novel sulfonamide analogues of 6/7-aminoflavones as anticancer agents via topoisomerase II inhibition.

A series of new sulfonamide analogues of 6/7-aminoflavones were synthesized by using molecular hybridization approach. These new sulfonamide analogues were screened for antiproliferative activity against human hepatocellular carcinoma (HepG-2), human lung cancer cell line (A-549), human colorectal adenocarcinoma (Caco-2) cancer cell lines. Compounds 5p, 5q, 5t, 5v, 5w and 5x exhibited good anticancer activity against selected cancer cell lines.

N-Benzylation of 6-aminoflavone by reductive amination and efficient access to some novel anticancer agents via topoisomerase II inhibition.

Series of novel N-benzyl derivatives of 6-aminoflavone (9a-n) were synthesized and evaluated for anticancer and topoisomerase II enzyme inhibition activity. All the synthesized compounds were screened for in vitro anticancer activity against human breast cancer cell line (MCF-7) and human lung cancer cell line (A-549). Among the synthesized compounds, 9f and 9g were found to be the most potent anticancer agents against human breast cancer cell line (MCF-7) with IC values of 9.

Structure-Based Site of Metabolism (SOM) Prediction of Ligand for CYP3A4 Enzyme: Comparison of Glide XP and Induced Fit Docking (IFD).

Metabolism is one of the prime reasons where most of drugs fail to accomplish their clinical trials. The enzyme CYP3A4, which belongs to the superfamily of cytochrome P450 enzymes (CYP), helps in the metabolism of a large number of drugs in the body. The enzyme CYP3A4 catalyzes oxidative chemical processes and shows a very broad range of ligand specificity.

New amide linked dimeric 1,2,3-triazoles bearing aryloxy scaffolds as a potent antiproliferative agents and EGFR tyrosine kinase phosphorylation inhibitors.

A search for potent antiproliferative agents has prompted to design and synthesize aryloxy bridged and amide linked dimeric 1,2,3-triazoles (7a-j) by using 1,3-dipolar cycloaddition reaction between 2-azido-N-phenylacetamides (4a-e) and bis(prop-2-yn-1-yloxy)benzenes (6a-b) via copper (I)-catalyzed click chemistry approach with good to excellent yields. All the newly synthesized compounds have been screened for their in vitro antiproliferative activities against two human cancer cell lines. The compounds 7d, 7e, 7h, 7i and 7j have revealed promising antiproliferative activity against human breast cancer cell line (MCF-7), whereas, the compounds 7a, 7b, 7c, 7i and 7j were observed as potent antiproliferative agents against human lung cancer cell line (A-549).

Comparative metabolomics of scab-resistant and susceptible apple cell cultures in response to scab fungus elicitor treatment.

Apple scab disease caused by the fungus Venturia inaequalis is a devastating disease that seriously affects quality and yield of apples. In order to understand the mechanisms involved in scab resistance, we performed gas chromatography-mass spectrometry based metabolomics analysis of the cell culture of scab resistant cultivar 'Florina' and scab susceptible cultivar 'Vista Bella' both prior -to and -following treatment with V. inaequalis elicitor (VIE).

Molecular cloning and functional analysis of a biphenyl phytoalexin-specific O-methyltransferase from apple cell suspension cultures.

This manuscript describes the cloning and functional characterization of a biphenyl phytoalexin biosynthetic gene, 3,5-dihydroxybiphenyl O-methyltransferase from elicitor-treated cell cultures of scab resistant apple cultivar 'Florina'. Apples belong to the subtribe Malinae of the Rosaceae family. Biphenyls and dibenzofurans are the specialized phytoalexins of Malinae, of which aucuparin is the most widely distributed biphenyl.

Ionic Liquid-Promoted Synthesis of Novel Chromone-Pyrimidine Coupled Derivatives, Antimicrobial Analysis, Enzyme Assay, Docking Study and Toxicity Study.

Herein, we report an environmentally friendly, rapid, and convenient ionic liquid ([Et₃NH][HSO₄])-promoted facile synthesis of ethyl 4-(6-substituted-4-oxo-4H-chromen-3-yl)-6-methyl-2-thioxo/oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives (-) and 4-(6-substituted-4-oxo-4H-chromen-3-yl)-6-methyl-2-thioxo/oxo-1,2,3,4-tetrahydropyrimidine-5- carbohydrazide derivatives (-). All the synthesized derivatives (-) and (-) were evaluated for their antifungal and antibacterial activity, by method recommended by National Committee for Clinical Laboratory Standards (NCCLS). The compound bearing a fluoro group on the chromone ring and oxygen and a hydrazino group (-NHNH₂) on the pyrimidine ring, was found to be the most potent antibacterial compound amongst the synthesized derivatives.

Salicylaldehyde synthase activity from Venturia inaequalis elicitor-treated cell culture of apple.

Salicylic acid (SA) is known to trigger a number of plant defense responses upon pathogen attack. It is well known that apple (Malus domestica) plants respond to pathogen invasion by synthesizing SA, but its biosynthesis is not well understood. In this study, we report salicylaldehyde synthase (SAS) activity from Venturia inaequalis elicitor (VIE)-treated cell suspension cultures of apple (Malus domestica 'Florina').

Novel 2-(nitrooxy)ethyl 2-(4-(substituted phenyl)-2-((substituted phenyl)amino)thiazol-5-yl)acetate as Anti-inflammatory, Analgesic and Nitric Oxide Releasing Agents: Synthesis and Molecular Docking Studies.

Background: Due to the need and adverse effects associated with the available anti-inflammatory agents, an attempt was made to develop the new anti-inflammatory agents with better activity and lesser adverse effects.

Objective: Synthetic approaches based on chemical modification of NSAIDs have been undertaken with the aim of improving NSAIDs safety profile.

Method: In the present study, a series of thiazole derivatives (3a-3x) was synthesized and tested for its anti-inflammatory with analgesic and nitric oxide releasing properties.

Facile Synthesis of Novel Coumarin Derivatives, Antimicrobial Analysis, Enzyme Assay, Docking Study, ADMET Prediction and Toxicity Study.

The work reports the synthesis under solvent-free condition using the ionic liquid [Et₃NH][HSO₄] as a catalyst of fifteen novel 3-((dicyclohexylamino)(substituted phenyl/heteryl)-methyl)-4-hydroxy-2-chromen-2-onederivatives - as potential antimicrobial agents. The structures of the synthesized compounds were confirmed by IR, ¹H-NMR, C-NMR, mass spectral studies and elemental analyses. All the synthesized compounds were evaluated for their antifungal and antibacterial activity.

Microwave-Assisted Facile Synthesis, Anticancer Evaluation and Docking Study of N-((5-(Substituted methylene amino)-1,3,4-thiadiazol-2-yl)methyl) Benzamide Derivatives.

In the present work, 12 novel Schiff's bases containing a thiadiazole scaffold and benzamide groups coupled through appropriate pharmacophore were synthesized. These moieties are associated with important biological properties. A facile, solvent-free synthesis of a series of novel (-) -((5-(substituted methylene amino)-1,3,4-thiadiazol-2-yl)methyl) benzamide was carried out under microwave irradiation.

Investigation of mitigating effect of colon-specific prodrugs of boswellic acid on 2,4,6-trinitrobenzene sulfonic acid-induced colitis in Wistar rats: Design, kinetics and biological evaluation.

Aim: To develop a colon-targeting bioreversible delivery system for β-boswellic acid (BBA) and explore utility of its prodrugs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.

Methods: Synthesis of 4 co-drugs of BBA with essential amino acids was achieved by CDI coupling, followed by their spectral characterization. kinetics were studied by HPLC in aqueous buffers, homogenates of gastrointestinal tract and fecal matter.