AI-DPAPT: a machine learning framework for predicting PROTAC activity.

Proteolysis Targeting Chimeras are part of targeted protein degradation (TPD) techniques, which are significant for pharmacological and therapy development. Small-molecule interaction with the targeted protein is a complicated endeavor and a challenge to predict the proteins accurately. This study used machine learning algorithms and molecular fingerprinting techniques to build an AI-powered PROTAC Activity Prediction Tool that could predict PROTAC activity by examining chemical structures. The chemical structures of a diverse set of PROTAC drugs and their corresponding activities are selected as a dataset for training the tool. The processes used in this study included data preparation, feature extraction, and model training. Further, evaluation was done for the performance of the various classifiers, such as AdaBoost, Support Vector Machine, Random Forest, Gradient Boosting, and Multi-Layer Perceptron. The findings show that the methods selected here depict accurate PROTAC activities. All the models in this study showed an ROC curve better than 0.9, while the random forest on the test set of the AI-DPAPT had an area under the curve score of 0.97, thus showing accurate results. Furthermore, the study revealed significant insights into the molecular features that can influence the functions of the PROTAC. These findings can potentially increase the understanding of the structure-activity correlations involved in the TPD. Overall, the investigation contributes to computational drug development by introducing this platform powered by artificial intelligence that predicts the function of PROTAC. In addition, it sped up the processes of identifying and improving previously unknown medications. The AI-DPAPT platform can be accessed online using a web server at https://ai-protac.streamlit.app/ .

Analyzing energetics and dynamics of hepatitis C virus polymerase interactions with marine bacterial compounds: a computational study.

Hepatitis C Virus (HCV) is a significant health concern affecting a large portion of the global population and is a major cause of acute liver diseases, including cirrhosis. The variability in the HCV genome mainly results from the rapid replication facilitated by the NS5B polymerase, making it a prime target for anti-HCV drug development. This study explores potential compounds from marine bacteria that could inhibit the HCV NS5B polymerase by virtual screening, analyzing the energetics, and dynamic behavior of target-compound complexes. Virtual screening with the Lipinski filter was employed to select compounds from the marine bacteria database that demonstrated strong binding affinity to NS5B. The top four (CMNPD27216, CMNPD21066, CMNPD21065, and CMNPD27283) compounds, ranked by their re-docking scores, underwent additional evaluation. Molecular dynamics simulations for 200 ns were conducted to assess the dynamic stability of these complexes in a solvent environment. Furthermore, methods such as MM-GBSA, PCA, and free energy landscape analysis were used to analyze the system's energetics and identify stable conformations by locating transition states. The findings suggest that these compounds exhibit promising binding capabilities to HCV polymerase and could be considered for future experimental validation.

Sinefungin analogs targeting VP39 methyltransferase as potential anti-monkeypox therapeutics: a multi-step computational approach.

The increasing spread of the Monkeypox virus (MPXV) presents a significant public health challenge, emphasising the urgent requirement for effective treatments. Our study focuses on the VP39 Methyltransferase enzyme of MPXV as a critical target for therapy. By utilising virtual screening, we investigated natural compounds with structural similarities to sinefungin, a broad-acting MTase inhibitor. From an initial set of 177 compounds, we identified three promising compounds-CNP0346326, CNP0343532, and CNP008361, whose binding scores were notably close to that of sinefungin. These candidates bonded strongly to the VP39 enzyme, hinting at a notable potential to impede the virus. Our rigorous computational assays, including re-docking, extended molecular dynamics simulations, and energetics analyses, validate the robustness of these interactions. The data paint a promising picture of these natural compounds as front-runners in the ongoing race to develop MPXV therapeutics and set the stage for subsequent empirical trials to refine these discoveries into actionable medical interventions.

Synthesis, In vitro and In silico Studies of Novel Bis-triazolopyridopyrimidines from Curcumin Analogues as Potential Aromatase Agents.

Breast cancer remains a major global health issue, particularly affecting women and contributing significantly to mortality rates. Current treatments for estrogen receptor-positive breast cancers, such as aromatase inhibitors, are effective but often come with side effects and resistance issues. This study addresses these gaps by targeting aromatase, an enzyme crucial for estrogen synthesis, which plays a pivotal role in breast cancer progression. The innovative approach involves synthesizing novel bis-triazolopyridopyrimidines, designed to leverage the combined pharmacological benefits of pyridopyrimidine and 1,2,4-triazole structures, known for their potent aromatase inhibition and anti-cancer properties. These compounds were synthesized and characterized using 1H-NMR, 13C-NMR, and MS spectral analyses, and their anticancer efficacy was evaluated through MTT assays against MCF-7 breast cancer cell lines in vitro. Molecular docking analyses revealed strong binding energies with aromatase, particularly for compounds 5 b, 5 c, 10 a, and 10 b, indicating their potential as effective aromatase inhibitors. The study highlights these compounds as promising candidates for further development as therapeutic agents against breast cancer.

Synthesis, Molecular Docking, and Dynamic Simulation Targeting Main Protease (Mpro) of New, Thiazole Clubbed Pyridine Scaffolds as Potential COVID-19 Inhibitors.

Many biological activities of pyridine and thiazole derivatives have been reported, including antiviral activity and, more recently, as COVID-19 inhibitors. Thus, in this paper, we designed, synthesized, and characterized a novel series of N-aminothiazole-hydrazineethyl-pyridines, beginning with a N'-(1-(pyridine-3-yl)ethylidene)hydrazinecarbothiohydrazide derivative and various hydrazonoyl chlorides and phenacyl bromides. Their Schiff bases were prepared from the condensation of N-aminothiazole derivatives with 4-methoxybenzaldehyde. FTIR, MS, NMR, and elemental studies were used to identify new products. The binding energy for non-bonding interactions between the ligand (studied compounds) and receptor was determined using molecular docking against the SARS-CoV-2 main protease (PDB code: 6LU7). Finally, the best docked pose with highest binding energy (8a = -8.6 kcal/mol) was selected for further molecular dynamics (MD) simulation studies to verify the outcomes and comprehend the thermodynamic properties of the binding. Through additional in vitro and in vivo research on the newly synthesized chemicals, it is envisaged that the achieved results will represent a significant advancement in the fight against COVID-19.

Potential anti-obesity/inflammatory flavonoid-derived biomolecules against Obesity to prevent WAT differentiation by targeting a DNA-binding protein inhibitor, ID-1.

A concoction of unhealthy eating, inactivity, and the adverse effects of specific drugs brings on obesity. The primary cause of Obesity is the storage of too much energy and triglycerides in adipocytes, particularly white adipose tissue (WAT). In addition to modifying one's lifestyle, anti-obesity medicines are increasingly used as adjuvant therapy. Flavonoids are the major class of compounds having significant biological impacts and health-improving properties. To find novel flavonoid compounds that fight obesity using computational drug design techniques. This work targets 1DI protein to predict new flavonoid compounds that fight obesity. The study uses computational approaches to anticipate potential anti-obesity/inflammatory flavonoid compounds against obesity to prevent WAT differentiation by targeting ID-1, a DNA-binding protein inhibitor. Our study led to the identification of the protein target inhibitor lead CID: 5280443, which was found to be a potent inhibitor of the receptor. According to the findings of this study, this bio-active molecule may be used as a lead for the development of drugs that preferentially fight obesity without interfering with the functions of the human proteasome. The scientific community will benefit from these discoveries, which could aid in the creation of new medications that treat obesity more successfully.

Targeting Breast Cancer Signaling via Phytomedicine and Nanomedicine.

BACKGROUND: The development of breast cancer (BC) and how it responds to treatment have both been linked to the involvement of inflammation. Chronic inflammation is critical in carcinogenesis, leading to elevated DNA damage, impaired DNA repair machinery, cell growth, apoptosis, angiogenesis, and invasion. Studies have found several targets that selectively modulate inflammation in cancer, limit BC's growth, and boost treatment effectiveness. Drug resistance and the absence of efficient therapeutics for metastatic and triple-negative BC contribute to the poor outlook of BC patients. SUMMARY: To treat BC, small-molecule inhibitors, phytomedicines, and nanoparticles are conjugated to attenuate BC signaling pathways. Due to their numerous target mechanisms and strong safety records, phytomedicines and nanomedicines have received much attention in studies examining their prospects as anti-BC agents by such unfulfilled demands. KEY MESSAGES: The processes involved in the affiliation across the progression of tumors and the spread of inflammation are highlighted in this review. Furthermore, we included many drugs now undergoing clinical trials that target cancer-mediated inflammatory pathways, cutting-edge nanotechnology-derived delivery systems, and a variety of phytomedicines that presently address BC.

In Vivo and In Silico Analgesic Activity of Ficus populifolia Extract Containing 2-O-ß-D-(3',4',6'-Tri-acetyl)-glucopyranosyl-3-methyl Pentanoic Acid.

Natural product-based structural templates have immensely shaped small molecule drug discovery, and new biogenic natural products have randomly provided the leads and molecular targets in anti-analgesic activity spheres. Pain relief achieved through opiates and non-steroidal anti-inflammatory drugs (NSAIDs) has been under constant scrutiny owing to their tolerance, dependency, and other organs toxicities and tissue damage, including harm to the gastrointestinal tract (GIT) and renal tissues. A new, 3',4',6'-triacetylated-glucoside, 2-O-ß-D-(3',4',6'-tri-acetyl)-glucopyranosyl-3-methyl pentanoic acid was obtained from Ficus populifolia, and characterized through a detailed NMR spectroscopic analysis, i.e., 1H-NMR, 13C-DEPT-135, and the 2D nuclear magnetic resonance (NMR) correlations. The product was in silico investigated for its analgesic prowess, COX-2 binding feasibility and scores, drug likeliness, ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties, possible biosystem's toxicity using the Discovery Studio®, and other molecular studies computational software programs. The glycosidic product showed strong potential as an analgesic agent. However, an in vivo evaluation, though at strong levels of pain-relieving action, was estimated on the compound's extract owing to the quantity and yield issues of the glycosidic product. Nonetheless, the F. populifolia extract showed the analgesic potency in eight-week-old male mice on day seven of the administration of the extract's dose in acetic acid-induced writhing and hot-plate methods. Acetic acid-induced abdominal writhing for all the treated groups decreased significantly (p < 0.0001), as compared to the control group (n = 6) by 62.9%, 67.9%, and 70.9% of a dose of 100 mg/kg (n = 6), 200 mg/kg (n = 6), and 400 mg/kg (n = 6), respectively. Similarly, using the analgesia meter, the reaction time to pain sensation increased significantly (p < 0.0001), as compared to the control (n = 6). The findings indicated peripheral and central-nervous-system-mediated analgesic action of the product obtained from the corresponding extract.

Synthesis, Molecular Docking Study, and Cytotoxicity Evaluation of Some Novel 1,3,4-Thiadiazole as Well as 1,3-Thiazole Derivatives Bearing a Pyridine Moiety.

Pyridine, 1,3,4-thiadiazole, and 1,3-thiazole derivatives have various biological activities, such as antimicrobial, analgesic, anticonvulsant, and antitubercular, as well as other anticipated biological properties, including anticancer activity. The starting 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)-3-phenylthiourea (2) was prepared and reacted with various hydrazonoyl halides 3a-h, α-haloketones 5a-d, 3-chloropentane-2,4-dione 7a and ethyl 2-chloro-3-oxobutanoate 7b, which afforded the 3-aryl-5-substituted 1,3,4-thiadiazoles 4a-h, 3-phenyl-4-arylthiazoles 6a-d and the 4-methyl-3- phenyl-5-substituted thiazoles 8a,b, respectively. The structures of the synthesized products were confirmed by spectral data. All of the compounds also showed remarkable anticancer activity against the cell line of human colon carcinoma (HTC-116) as well as hepatocellular carcinoma (HepG-2) compared with the Harmine as a reference under in vitro condition. 1,3,4-Thiadiazole 4h was found to be most promising and an excellent performer against both cancer cell lines (IC50 = 2.03 ± 0.72 and 2.17 ± 0.83 µM, respectively), better than the reference drug (IC50 = 2.40 ± 0.12 and 2.54 ± 0.82 µM, respectively). In order to check the binding modes of the above thiadiazole derivatives, molecular docking studies were performed that established a binding site with EGFR TK.

Facile Synthesis of ZIF-67 for the Adsorption of Methyl Green from Wastewater: Integrating Molecular Models and Experimental Evidence to Comprehend the Removal Mechanism.

Organic dyes with enduring colors which are malodorous are a significant source of environmental deterioration due to their virulent effects on aquatic life and lethal carcinogenic effects on living organisms. In this study, the adsorption of methyl green (MG), a cationic dye, was achieved by using ZIF-67, which has been deemed an effective adsorbent for the removal of contaminants from wastewater. The characterization of ZIF-67 was done by FTIR, XRD, and SEM analysis. The adsorption mechanism and characteristics were investigated with the help of control batch experiments and theoretical studies. The systematical kinetic studies and isotherms were sanctioned with a pseudo-second-order model and a Langmuir model (R2 = 0.9951), confirming the chemisorption and monolayer interaction process, respectively. The maximum removal capacities of ZIF-67 for MG was 96% at pH = 11 and T = 25 °C. DFT calculations were done to predict the active sites in MG by molecular electrostatic potential (MEP). Furthermore, both Molecular dynamics and Monte Carlo simulations were also used to study the adsorption mechanism.

Microwave-Assisted One Pot Three-Component Synthesis of Novel Bioactive Thiazolyl-Pyridazinediones as Potential Antimicrobial Agents against Antibiotic-Resistant Bacteria.

Pyridazine and thiazole derivatives have various biological activities such as antimicrobial, analgesic, anticancer, anticonvulsant, antitubercular and other anticipated biological properties. Chitosan can be used as heterogeneous phase transfer basic biocatalyst in heterocyclic syntheses. Novel 1-thiazolyl-pyridazinedione derivatives were prepared via multicomponent synthesis under microwave irradiation as ecofriendly energy source and using the eco-friendly naturally occurring chitosan basic catalyst with high/efficient yields and short reaction time. All the prepared compounds were fully characterized by spectroscopic methods, and their in vitro biological activities were investigated. The obtained results were compared with those of standard antibacterial/antifungal agents. DFT calculations and molecular docking studies were used to investigate the electronic properties and molecular interactions with specific microbial receptors.

GC-MS analysis, molecular docking, and pharmacokinetic studies of Multidentia crassa extracts' compounds for analgesic and anti-inflammatory activities in dentistry.

Plant extracts have been useful for oral health or dentistry. However, only a few evidence-based justifications exist. This study evaluated Multidentia crassa (Hiern) Bridson & Verdc, one of the oral health-used plants in Malawi. Gas chromatography-mass spectrometry (GC-MS) and Fourier transform infrared (FT-IR) identified the extracts' compounds. The pharmacokinetics of the identified compounds were studied using pkCSM and SwissADME, and molecular docking studies were used to identify potential drug candidates for oral health by predicting the binding affinity of the compounds to cyclooxygenases, interleukin-1 beta receptors, odontoblast cold sensor proteins, and purinergic receptor P2X3. FT-IR analysis showed characteristic peaks of phenols, carboxylic acids, alkenes, alkyl halides, amines, esters, ethers, aromatics, and lipids. GC-MS results showed the presence of 58 bioactive phytocompounds, some of which have various pharmacological activities relevant to oral health. Molecular docking further validated stigmastan-3,5-diene's potency for analgesic and anti-inflammatory purposes. Based on a literature review, this is the first report on the bioactive compounds of M. crassa extracts showing analgesic and anti-inflammatory effects. This study's results can lead to new herbal and conventional medicines. Therefore, we recommend in vivo and in vitro studies to elucidate the pharmacological effects of the plant extracts.

Structural and free energy landscape analysis for the discovery of antiviral compounds targeting the cap-binding domain of influenza polymerase PB2.

Influenza poses a significant threat to global health, with the ability to cause severe epidemics and pandemics. The polymerase basic protein 2 (PB2) of the influenza virus plays a crucial role in the viral replication process, making the CAP-binding domain of PB2 an attractive target for antiviral drug development. This study aimed to identify and evaluate potential inhibitors of the influenza polymerase PB2 CAP-binding domain using computational drug discovery methods. We employed a comprehensive computational approach involving virtual screening, molecular docking, and 500 ns molecular dynamics (MD) simulations. Compounds were selected from the Diverse lib database and assessed for their binding affinity and stability in interaction with the PB2 CAP-binding domain. The study utilized the generalized amber force field (GAFF) for MD simulations to further evaluate the dynamic behaviour and stability of the interactions. Among the screened compounds, compounds 1, 3, and 4 showed promising binding affinities. Compound 4 demonstrated the highest binding stability and the most favourable free energy profile, indicating strong and consistent interaction with the target domain. Compound 3 displayed moderate stability with dynamic conformational changes, while Compound 1 maintained robust interactions throughout the simulations. Comparative analyses of these compounds against a control compound highlighted their potential efficacy. Compound 4 emerged as the most promising inhibitor, with substantial stability and strong binding affinity to the PB2 CAP-binding domain. These findings suggest that compound 4, along with compounds 1 and 3, holds the potential for further development into effective antiviral agents against influenza. Future studies should focus on experimental validation of these compounds and exploration of resistance mechanisms to enhance their therapeutic utility.

Unraveling the therapeutic potential of Satureja nabateorum extract: inducing apoptosis and cell cycle arrest through p53, Bax/Bcl-2, and caspase-3 pathways in human malignant cell lines, with in silico insights.

Satureja nabateorum, known as Nabatean savory is a Lamiaceae plant native to the Arabian Peninsula, specifically in the mountainous regions of Saudi Arabia. The study aims to investigate the phytochemical components of the S. nabateorum leaves (SNL) and stems (SNS) extract and to assess their antioxidant, antimicrobial, and antiproliferative properties. Methanol extracts from leaves and stems were analyzed for chemical constituents using the GC-MS technique. Antioxidant capacities were measured using hydrogen peroxide and ABTS radical-scavenging methods, and antimicrobial activity was tested against various microorganisms. Cytotoxic activity on four human malignant cell lines was assessed using MTT and flow cytometry. Molecular docking and molecular dynamics studies were conducted to understand the interactions and binding modes of the extracted compounds at a molecular level. GC-MS analysis of SNL extract revealed thymol, carvacrol, and p-cymen-8-ol as major constituents. SNS extract contained ß-sitosterol, stigmasterol, lupeol, and lup-20(29)-ene-3ß,28-diol. SNS extract exhibited more potent antioxidant, antimicrobial, and anticancer effects than SNL extract. The extract, SNS, exhibited potential toxicity in A549 cells with an IC50 value of 3.62 µg/mL and induced marked apoptotic effects with S phase-cell cycle arrest. SNS extract also showed higher levels of Caspase 3, Bax, p53, and the Bax/Bcl2 ratio and lower levels of Bcl-2. Molecular docking and dynamic simulation supported these findings, targeting the EGFR TK domain. The study suggests that the S. nabateorum stem extract holds promise as a potent antimicrobial, antioxidant, and anticancer agent. It provides valuable insights for considering the extract as a substitute for chemotherapy and/or protective agents.

Phytochemical composition, in vitro cytotoxicity, and in silico docking properties of Tamarix tetragyna L.

Tamarix tetragyna is a plant grows in Mediterranean area and some Arab countries. It possesses numerous medicinal values. Purpose of our study is to explore biological activity of tamarix tetragyna extracts of both leaves and stem with investigating their phytochemical composition. The investigated extracts' phyto-constituent composition was determined using gas chromatographic-mass spectrometric method. In addition, in vitro cytoxicity activity versus cancer cell lines such MCF-7, HepG-2, HCT-116, and A-549 was examined by MTT assay method, together with exploring its apoptosis effect by flow cytometry and western blot analysis techniques. Moreover, some phytochemical compounds were identified, and in-silico evaluated against anticancer molecular targets. Plant extracts showed good cytotoxic activity against both A-549 and HCT-116 cancer cell lines. With an IC50 value of 23.90 µg/ml that led to apoptosis and G2/M-phase arrest in A-549 cells, cytotoxicity data demonstrate leaves' extract effectiveness against these cells. Upon GC-MS analysis, it revealed presence of some bioactive components such as Stigmast-5-en-3-ol and 2-methoxy-4-vinyl phenol, which are known for their cytotoxic activity. Our findings suggest that methanolic extracts of Tamarix tetragyna parts may have potential therapeutic uses as anticancer against A-549 cells, which opens up further avenues for investigation into its industrial applications.

Synthesis and evaluation of pyridine-3-carboxamide analogs as effective agents against bacterial wilt in tomatoes.

This study focused on developing novel pyridine-3-carboxamide analogs to treat bacterial wilt in tomatoes caused by Ralstonia solanacearum. The analogs were synthesized through a multistep process and their structures confirmed using spectroscopy. Molecular docking studies identified the most potent analog from the series. A specific analog, compound 4a, was found to significantly enhance disease resistance in tomato plants infected with R. solanacearum. The structure-activity relationship analysis showed the positions and types of substituents on the aromatic rings of compounds 4a-i strongly influenced their biological activity. Compound 4a, with a chloro group at the para position on ring C and hydroxyl group at the ortho position on ring A, was exceptionally effective against R. solanacearum. When used to treat seeds, the analogs displayed remarkable efficacy, especially compound 4a which had specific activity against bacterial wilt pathogens. Compound 4a also promoted vegetative and reproductive growth of tomato plants, increasing seed germination and seedling vigor. In plants mechanically infected with bacteria, compound 4a substantially reduced the percentage of infection, pathogen quantity in young tissue, and disease progression. The analogs were highly potent due to their amide linkage. Molecular docking identified the best compounds with strong binding affinities. Overall, the strategic design and synthesis of these pyridine-3-carboxamide analogs offers an effective approach to targeting and controlling R. solanacearum and bacterial wilt in tomatoes.

Novel landmarks on the journey from natural products to pharmaceutical formulations: Phytochemical, biological, toxicological and computational activities of Satureja hortensis L.

This study examined the ethanolic extract of the Satureja hortensis L. plant's aerial parts to describe its phytochemical makeup, biological functions, toxicity tests, and in-silico molecular docking tests. The GC-MS analysis was used to evaluate the phytochemical composition of the tested extract, and the ABTS and hydrogen peroxide antioxidant assays were used to measure antioxidant activity. Aspergillus fumigatus, Candida albicans, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Proteus vulgaris were tested for antimicrobial potential. On cell lines such as HepG-2, MCF-7, A-549, and Panc-1, the in-vitro toxicity was also examined. The A-549 cell line was also used for flow cytometry analysis of apoptosis and cell cycle. Additionally, the compounds discovered by the GC-MS analysis were used in silico tests against biological targets. Eight different phytocompounds were tentatively identified as a result of the GC-MS analysis. The compounds also demonstrated significant antioxidant potential for the ABTS and H2O2 assays (IC50: 2.44 and 28.04 µg/ml, respectively). The tested extract was found to have a range of inhibition zones and to be significantly active against the tested bacterial and fungal strains. Apoptosis and cell cycle analysis for the A-549 cell line showed that the cell cycle was arrested at S-phase, and the extract was also found to be most active against this cell line with an IC50 value of 113.05 µg/ml. The docking studies have emphasized the compounds' interactions and binding scores with the EGFR-TK target as determined by the GC-MS.

Investigating the bispecific lead compounds against methicillin-resistant Staphylococcus aureus SarA and CrtM using machine learning and molecular dynamics approach.

Methicillin-resistant Staphylococcus aureus (MRSA) is a notorious pathogen that has emerged as a serious global health concern over the past few decades. Staphylococcal accessory regulator A (SarA) and 4,4'-diapophytoene synthase (CrtM) play a crucial role in biofilm formation and staphyloxanthin biosynthesis. Thus, the present study used a machine learning-based QSAR model to screen 1261 plant-derived natural organic compounds in order to identify a medication candidate with both biofilm and virulence inhibitory potential. Additionally, the in-silico molecular docking analysis has demonstrated significant binding efficacy of the identified hit compound, that is 85137543, with SarA and CrtM when compared to the control compound, hesperidin. Post-MD simulation analysis of the complexes depicted strong binding of 85137543 to both SarA and CrtM. Moreover, 85137543 showed hydrogen bonding with the key residues of both proteins during docking (ALA138 of SarA and ALA134 of CrtM) and post-MD simulation (LYS273 of CrtM and ASN212 of SarA). The RMSD of 85137543 was stable and consistent when bound to both CrtM and SarA with RMSDs of 1.3 and 1 nm, respectively. In addition, principal component analysis and the free energy landscape showed stable complex formation with both proteins. Low binding free energy (ΔGTotal) was observed by 85137543 for SarA (-47.92 kcal/mol) and CrtM (-36.43 kcal/mol), which showed strong binding. Overall, this study identified 85137543 as a potential inhibitor of both SarA and CrtM in MRSA.Communicated by Ramaswamy H. Sarma.

Synthesis, Biological Evaluation, and Molecular Docking of Novel Azolylhydrazonothiazoles as Potential Anticancer Agents.

A novel set of thiazolylhydrazonothiazoles bearing an indole moiety were synthesized by subjection reactions of carbothioamide derivative and hydrazonoyl chlorides (or α-haloketones). The cytotoxicity of the synthesized compounds was evaluated against the colon carcinoma cell line (HCT-116), liver carcinoma cell line (HepG2), and breast carcinoma cell line (MDA-MB-231), and demonstrated encouraging activity. Furthermore, when representative products were assessed for toxicity against normal cells, minimal toxic effects were observed, indicating their potential safety for use in pharmacological studies. The mechanism of action of the tested products, as inhibitors of the epidermal growth factor receptor tyrosine kinase domain (EGFR TK) protein, was suggested through docking studies that assessed their binding scores and modes, in comparison to a reference standard (W19), thus endorsing their anticancer activity.

Green Synthesis of Zinc Oxide Nanoparticles Using Cymbopogon citratus Extract and Its Antibacterial Activity.

Excessive use of antimicrobial medications including antibiotics has led to the emerging menace of antimicrobial resistance, which, as per the World Health Organization (WHO), is among the top ten public health threats facing humanity, globally. This necessitates that innovative technologies be sought that can aid in the elimination of pathogens and hamper the spread of infections. Zinc oxide (ZnO) has multifunctionality owing to its extraordinary physico-chemical properties and functionality in a range of applications. In this research, ZnO nanoparticles (NPs) were synthesized from zinc nitrate hexahydrate, by a green synthesis approach using Cymbopogon citratus extract followed by characterization of the NPs. The obtained X-ray diffraction peaks of ZnO NPs matched with the standard JCPDS card (no. 89-510). The particles had a size of 20-24 nm, a wurtzite structure with a high crystallinity, and hexagonal rod-like shape. UV-Vis spectroscopy revealed absorption peaks between 369 and 374 nm of ZnO NPs synthesized from C. citratus extract confirming the formation of ZnO. Fourier transform infrared confirmed the ZnO NPs as strong absorption bands were observed in the range of 381-403 cm-1 corresponding to Zn-O bond stretching. Negative values of the highest occupied molecular orbital-lowest unoccupied molecular orbital for ZnO NPs indicated the good potential to form a stable ligand-protein complex. Docking results indicated favorable binding interaction between ZnO and DNA gyrase subunit b with a binding energy of -2.93 kcal/mol. ZnO NPs at various concentrations inhibited the growth of Escherichia coli and Staphylococcus aureus. Minimum inhibitory concentration values of ZnO NPs against E. coli and S. aureus were found to be 92.07 ± 0.13 and 88.13 ± 0.35 µg/mL, respectively, at a concentration of 2 mg/mL. AO/EB staining and fluorescence microscopy revealed the ability of ZnO NPs to kill E. coli and S. aureus cells. Through the findings of this study, it has been shown that C. citratus extract can be used in a green synthesis approach to generate ZnO NPs, which can be employed as alternatives to antibiotics and a tool to eliminate drug-resistant microbes in the future.