The biggest cause of cancer deaths globally was lung cancer. New cancer fighting drugs are needed due to the rising number of cancer patients and cancer cells' treatment resistance. Two Cu(II) complexes, synthesized from ligands based on 2-aminomethyl benzimidazole and salicylaldehyde derivatives, were designed and evaluated for their effectiveness against A549 lung cancer. The compounds were subjected to computational calculation using Density Functional Theory (DFT) to gather information on their reactivity. Furthermore, molecular docking are utilized to simulate the interaction between the compound and the MPP-9 protein. The synthesis of the ligands and their Cu(II) metal complexes are efficient and straightforward. The complexation between copper atom and the ligand are in 1:1 ratio. The MTT assay of the compounds against A549 lung carcinoma reveals that the both Cu(II) complexes good cytotoxicity activity, in comparison to their respective ligands. The low HOMO-LUMO band gap based on the DFT calculation predicts the high reactivity of the compounds. Furthermore, the low binding energy and the numbers of interactions of the Cu(II) complexes with MMP-9 protein binding site coincide with the antiproliferative activity tested . The cytotoxicity studies performed for Cu(L1Br) are promising, indicating a good candidate for a future drug.

The aim of this study is to synthesize indolo[2,3-]quinoxaline-4-aminoquinoline-based hybrids and evaluate their effectiveness against chloroquine-susceptible (3D7) and resistant (W2) strains, with expected inhibition of chloroquine resistance transporter (CRT) and heme. The hybrids were synthesized and evaluated against both susceptible and resistant strains. Molecular docking and studies were conducted to assess the binding affinities for the CRT protein. Additionally, heme-inhibition studies using hemin chloride provided valuable insights into the interaction between the ligand and heme. The binding constant (logK) was calculated, providing quantitative details about the strength of this interaction. The synthesized hybrids showed reasonable potency against both strains. The most potent hybrid , with fluorine-substitution exhibited good activity. Molecular docking studies indicated strong binding affinities for the CRT protein. Heme inhibition studies further supported the potential of as an effective anti-plasmodial agent.

Quinoline scaffolds are serving as the core structure for numerous antifungal, analgesic, antipyretic, anti-inflammatory drugs as well as have also been investigated for their potential antidiabetic properties. Though further exploration is required in this area as the current antidiabetic agents, such as acarbose, miglitol and voglibose, are associated with several adverse side effects. In this context, arylated tetrahydrobenzo[]quinoline-3-carbonitrile derivatives were designed and evaluated as potential antidiabetic agents. A one-pot multicomponent reaction of 6-methoxy-1-tetralone with ethyl cyanoacetate, ammonium acetate and varying aldehydes yielded a range of new arylated tetrahydrobenzo[]quinoline-3-carbonitrile molecules . Compounds , , , and showed excellent inhibition against α-amylase (IC = 3.42-15.14 μM) and α-glucosidase (IC = 0.65-9.23 μM) enzymes in comparison to the standard acarbose (IC = 14.35 μM). In addition, all compounds revealed significant to moderate DPPH radical scavenging activity (SC = 21.30-138.30 μM) compared with BHT (SC = 64.40 μM). Kinetic studies confirmed competitive inhibition mode, while molecular docking studies comprehend ligands' interaction with enzyme's active sites and absorption, distribution, metabolism, and excretion analysis confirms that all synthetic derivatives are nontoxic. This research offers a range of lead candidates to become antidiabetic agents after further advanced study.

KRAS is the most commonly mutated isoform in RAS-driven cancers. In the early stage, KRAS was deemed as an "undruggable" cancer target due to the lack of suitable binding pockets. With the development of KRAS inhibitors in recent years, strategies that directly suppress oncogenic KRAS have achieved significant breakthroughs. In this review, we summarize recent advances in direct small-molecule KRAS inhibitors used for cancer therapy, highlighting their medicinal chemistry optimization processes. Moreover, new PROTACs targeting the KRAS mutation are also presented. Additionally, we put forward the challenges and prospects for the development of future KRAS inhibitors.

To develop a model for predicting the biological activity of compounds targeting the HIV-1 protease and to establish factors influencing enzyme inhibition. Machine learning models were built based on a combination of Richard Bader's theory of Atoms in Molecules and topological analysis of electron density using experimental x-ray 'protein-ligand' complexes and inhibition constants data. Among all the models tested, logistic regression achieved the highest accuracy of 0.76 on the test set. The model's ability to differentiate between less active and highly active classes was relatively good, as indicated by an AUC-ROC score of 0.77. The analysis identified several critical factors affecting the biological activity of HIV-1 protease inhibitors, including the electron density contribution of hydrogen atoms, bond-critical points and particular amino acid residues. These findings provide new insights into how these molecular factors influence HIV-1 protease inhibition, emphasizing the importance of hydrogen bonding, glycine's flexibility and hydrophobic interactions in ligand binding.

The structural optimization of our recently reported CDK9 inhibitor to furnish novel aminopyrazolones and methylpyrazolones with improved pharmacokinetics. The synthesis of the targeted compounds was accomplished via conventional, grinding and microwave-assisted processes. The cytotoxicity of them was assayed against three carcinomas. Analogs , and showed significant cytotoxicity and selectivity toward all tested cells. They also displayed potent CDK9 inhibition. Compound arrested MCF-7 cycle at G2/M phase by stimulating the apoptotic pathway. The biodistribution of radiolabeled compound displayed a potent targeting capability of I in solid tumors. Entity is a potent CDK9 inhibitor where I-compound can be used as a significant radiopharmaceutical imaging tool for tumors.

HS-1793 is a novel derivative of resveratrol, a compound known for its numerous beneficial effects, including anticancer activity, anti-inflammatory response, antimicrobial, antiaging, anti-cardiovascular disease activity, neuroprotective activity, etc. Despite its wide and interesting properties, resveratrol suffers from a crucial flaw because it is low bioavailable. For this reason, many other derivatives were explored and among them, HS-1793 has caught the attention of researchers. HS-1793 is a synthetic derivative of resveratrol discovered in 2007 that has been shown to have anti-cancer and anti-inflammatory properties. In addition, the compound showed a positive profile in metabolic processes, with adequate pharmacokinetics and pharmacodynamics. This review highlights current research on HS-1793, evaluating and works and lays the foundation for novel explorative trials in human diseases.

Nicotinamide-based VEGFR-2 inhibitors have good contribution in drug discovery. Development of novel nicotinamides as VEGFR-2 inhibitors. different and assays were conducted to evaluate the VEGFR-2 inhibition and cytotoxicity. Compound displayed strongest anti-VEGFR-2 potentiality and good anti-proliferative effects. Compound enhanced apoptosis and caused cell cycle arrest in the Pre-G1 and S phases. Compound boosted the level of the apoptotic caspase-3 and inhibited the level of TNF-α and IL-6 in tumor cells. Molecular docking and molecular dynamics (MD) simulations indicated the outstanding binding potential of compound against VEGFR-2. Compound is a good candidate for the creation of a novel antiangiogenic lead anticancer medication.

The main goal of this study was to synthesize new derivatives of 4-amino-3-chloro benzoate ester, including 1,3,4-oxadiazole derivatives (), benzohydrazone derivatives (), and hydrazine-1-carbothioamide derivatives () that target epidermal growth factor receptor (EGFR) tyrosine kinase.

The current research presents novel library of indole derived fused triazole-thiadiazole derivatives (1-17) for treatment of diabetes mellitus. These compounds were synthesized by treating 2-(1H-indol-3-yl)acetic acid with hydrazinecarbothiohydrazide followed by treating the resultant compound with substituted benzoic acid. Structural validation was achieved spectroscopically (HNMR, CNMR and HREI-MS). The synthesized compounds were subjected to biological evaluation to assess their potential as anti-diabetic. Molecular docking study was employed to investigate the binding interactions of these analogs with relevant proteins. ADMET analysis was used to predict their drug-like properties. Notably, compound- (IC = and μM) bearing -substituted F atom exhibited the highest potency due to strong inhibitory interactions through hydrogen bonding. This study identifies promising compounds with anti-diabetic activity, paving the way for the treatment of diabetes mellitus.

The current work is an extension to our previous work for the development of new thalidomide analogs. Quinazolinone-based molecules carrying a glutarimide moiety have been designed, synthesized and biologically evaluated for immunomodulatory and anticancer activity. Compounds and showed considerable immunomodulatory properties in comparison to thalidomide. and significantly reduced TNF-α levels in HepG-2 cells from 162.5 to 57.4 pg/ml and 49.2 pg/ml, respectively, compared with 53.1 pg/ml reported for thalidomide. Moreover, they caused 69.33 and 77.74% reduction in NF-κB P65, respectively, compared with 60.26% reduction for thalidomide. Similarly, they reduced VEGF from 432.5 to 161.3 pg/ml and 132.8 pg/ml, respectively, in comparison to 153.2 pg/ml reported for thalidomide. The two new derivatives, and also showed about eightfold increases in caspase-8 levels in cells treated with them. These results were slightly better than those of thalidomide. The obtained results revealed that Compound had better immunomodulatory properties than thalidomide, with stronger effects on TNF-α, NF-κB P65, VEGF and caspase-8. This work indicates that compounds and have interesting biological properties that should be further evaluated and modified in order to develop clinically useful thalidomide analogs.

-chalcone has emerged as a promising candidate for new therapeutic alternatives, owing to its pharmacological properties and potential in various medical areas. This study aimed to conduct a systematic review of articles, patents and clinical trials on -chalcone's applications and biological activities. The review proposed a thorough analysis of studies such as scientific articles, patents and clinical studies related to the topic. The searches were carried out in their respective databases and analyzed through the exclusion steps, until selecting studies that corroborate the importance of the topic. The review consolidated evidence from multiple studies, encompassing and methodologies across different conditions like cancer, leishmania, skin protection, inflammation and metabolic diseases. Patent analysis indicated growing interest from pharmaceutical companies and universities, suggesting diverse applications from chronic diseases to previously challenging conditions. Clinical trials utilizing -chalcone revealed insufficient investigation, crucial for obtaining essential pharmacokinetic and pharmacodynamic data. While positive results were noted, the review also identified knowledge gaps and areas needing further exploration. In summary, -chalcone holds promise for new therapies, supported by evidence from patents, clinical trials and systematic reviews, driving continued research and development in this field.

Diabetes is characterized by a lack of insulin and insensitivity to insulin. In 2013, the global diabetes population was 382 million, with 90% of them having type 2 diabetes (non-insulin-dependent). It is predicted that this number will increase to 592 million by 2035. Here, we aimed to synthesize a series of benzimidazole-based derivatives - with α-glucosidase inhibition potential as antidiabetic agents. Compounds - were prepared in three three-step reactions, and the structures were elucidated using spectroscopic methods, namely 1H NMR, 13C NMR, MS and IR. Enzyme inhibition and kinetic study were done using commercial assay kits, and molecular docking study using autodock4. Bioassay data showed that twenty-four out of the thirty-two tested compounds exhibited IC50 values ranging from 44 to 745 μM, surpassing the standard molecule, acarbose (IC50: 750 μM). it was determined that the best compound, , functions as a competitive inhibitor. Additionally, a molecular docking study provided insights into the interactions between the four most promising compounds (, , and ) and the active site residues within the enzyme. The tested compounds are interesting α-glucosidase inhibitors, which indicates the benefit of more bioassay studies, especially studies.

A series of (R)-Carvone-based 1,2,3-triazole-thiazolidinone hybrids were synthesized and characterized by spectroscopic techniques NMR and HRMS. The chemical reactivity and the stability parameters were observed via DFT. The objective was to evaluate the anticancer activity of the synthesized compounds against cancer cell lines. The mechanism of action by which the and exert their effect suggested that they may induce apoptosis through activation of caspase-3/7. This effect was observed against the most important NIMA-related kinases via Docking investigation. The designed compounds were identified as the best inhibitors of the NEK family via the inactivation of the caspase-3. The Docking results were supported by Dynamics where the binding energies justified the medicinal importance of the synthesized derivatives.

This work describes the synthesis and antimicrobial evaluation of 6-aminated 1,4-benzoquinones (6-AQs) against seven resistant pathogens. The 6-AQs, synthesized via a Michael addition reaction between bromoquinone and -substituted anilines, were assessed for their antimicrobial activity through both and analyses. Bromoquinone and 6-AQs with electron-withdrawing groups demonstrated activity against , with minimum inhibitory concentrations ranging from 16 to 128 μg/ml, comparable to standard antimicrobials. Two derivatives exhibited minimum inhibitory concentrations values against methicillin-resistant ranging from 64 to 128 μg/ml. These compounds demonstrated both bacteriostatic and bactericidal effects, and antibiofilm features. The 6-AQs and showed a promising antimicrobial profile, indicating their potential as new therapeutic options.

Breast cancer is the most recurring cancer among females and is being diagnosed as a major cause of death among women. Levosulpiride Schiff base derivatives were synthesized and analyzed by physical and spectral (FTIR, H-NMR, C-NMR) analysis. MTT assay against MCF-7 (human breast cancer cell line), scavenging activity and Molecular docking against receptors 1M17, 3PP0, 3IOK and 4KIK along ADME pharmacokinetic studies were performed. L1 and L3 synthesized derivatives have revealed better percent cell viability and inhibitory concentration (IC) with scavenging activity as of the parent compound. L1, L3 and L9 revealed significant docking scores compared with standard drugs. Most of the derivatives showed strong pharmacokinetic profiles while no drug crossed blood-brain barrier. The newly synthesized L1 and L3 levosulpiride-derived compounds have demonstrated promising anticancer properties against breast cancer cells.

The amination and cyclization method developed a new strategy for designing and assembling new 1,4-dihydropyridine derivatives of compounds 3a-g and 4a-g. Newly prepared pyridine compounds are more economical, and reduce the reaction time. FT-IR, H-NMR, 13C-NMR, mass spectroscopy and elemental analyses elucidated the synthesized derivatives. All the derivatives are subjected to assay against MCF-7 (breast) and anti-bacterial activity. In the anti-bacterial activity compound is moderately active against (6.0 g/ml), and is extremely active against Lactiplantibacillus (10.0 g/ml) compared with standard Erythromycin. In cytotoxic activity, the compound (lC50 24.5 μM) is slightly active against standard doxorubicin. We also present the outcome of a molecular docking study connecting the methoxsalen (Protein Data Bank, PDB ID: 1Z11). Compound shows a higher binding affinity (-7.7 Kcal/mol) matching up with doxorubicin(-9.0 Kcal/mol). The synthesized analogs were predicted for their adsorption, distribution, metabolism and excretion profiles and pharmacokinetics. The compound has three rotatable bonds (NROB≤10), five hydrogen bond acceptors (HBA≤10) and four hydrogen bond donors (HBD≤5). All the compounds follow Lipinski's rule. Therefore, the compounds and are used as cytotoxic and anti-bacterial drugs in feature.

Eugenol, a natural compound found in essential oils such as clove oil, has been extensively studied for its diverse biological activities including the therapeutic potential against microbial and parasitic infections. This review provides an overview of the synthetic strategies (shown in Supplementary Material) employed to develop bioactive derivatives and analogues derived from eugenol and related compounds (e.g., dihydroeugenol and isoeugenol), focusing on biological activity of more than 100 bioactive eugenol derivatives against bacterial, fungal, viral and protozoal pathogens. Through a comprehensive survey of literature, this paper shows the impact of structural modifications of these phenylpropanoids on antimicrobial and antiparasitic activity. Key findings highlight promising candidates for further development in antimicrobial drug discovery, suggesting directions for future research in the pursuit of effective therapeutic agents.