Good Docking Scores Research Articles

Headspace Solid Phase Micro-Extraction of Volatile Constituents Produced from Saudi Ruta chalepensis and Molecular Docking Study of Potential Antioxidant Activity.

Ruta chalepensis L., commonly known as Shazab in Saudi Arabia, is one of the famous culinary plants belonging to the Rutaceae family. It is commonly used in ethnomedicine in treating numerous diseases. This study was performed to characterize the essential oil isolated from Saudi species using a relatively new advanced headspace solid-phase microextraction technique. Following that, the antioxidant activity of the extracted oil was assessed using in vitro techniques such as the DPPH and nitric oxide scavenging tests, as well as the reducing power FRAP study and the molecular docking tool. The essential oil yield of the dried plant was 0.83% (v/w). Gas chromatography joined with a mass spectrometer was used to determine the chemical composition of the pale-yellow essential oil. Sixty-eight constituents were detected, representing 97.70% of the total oil content. The major constituents were aliphatic ketones dominated by 2-undecanone (37.30%) and 2-nonanone (20.00%), with minor constituents of mono and sesquiterpenoids chemical classes. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is one of the major causes of many contemporary diseases due to its ability to create a reactive oxygen species (ROS). Thus, molecular docking was used to confirm that some oil phytoconstituents have good docking scores compared to the standard antioxidant drug (Vitamin C), indicating great binding compatibility between the (NADPH) oxidase receptor site and the ligand. In conclusion, our findings suggest that the oil could be used safely and as a cost-effective remedy in treating various modern diseases caused by free radical formation.

Identification of Novel Natural Dual HDAC and Hsp90 Inhibitors for Metastatic TNBC Using e-Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Studies.

Breast cancer (BC) is one of the main types of cancer that endangers women's lives. The characteristics of triple-negative breast cancer (TNBC) include a high rate of recurrence and the capacity for metastasis; therefore, new therapies are urgently needed to combat TNBC. Dual targeting HDAC6 and Hsp90 has shown good synergistic effects in treating metastatic TNBC. The goal of this study was to find potential HDAC6 and Hsp90 dual inhibitors. Therefore, several in silico approaches have been used. An e-pharmacophore model generation based on the HDAC6-ligand complex and subsequently a pharmacophore-based virtual screening on 270,450 natural compounds from the ZINC were performed, which resulted in 12,663 compounds that corresponded to the obtained pharmacophoric hypothesis. These compounds were docked into HDAC6 and Hsp90. This resulted in the identification of three compounds with good docking scores and favorable free binding energy against the two targets. The top three compounds, namely ZINC000096116556, ZINC000020761262, and ZINC000217668954, were further subjected to ADME prediction and molecular dynamic simulations, which showed promising results in terms of pharmacokinetic properties and stability. As a result, these three compounds can be considered potential HDAC6 and Hsp90 dual inhibitors and are recommended for experimental evaluation.

Computational multi-target approach to target essential enzymes of Leishmania donovani using comparative molecular dynamic simulations and MMPBSA analysis.

Visceral leishmaniasis (VL) is caused by Leishmania donovani. The purine and pyrimidine pathways are essential for L. donovani. Simultaneously inhibiting multiple targets could be an effective strategy to eliminate the pathogen and treat VL. We aimed to target the essential enzymes of L. donovani and inhibit them using a multi-target approach. A systematic analytical method was followed, in which first reported inhibitors of two essential enzymes (adenine phosphoribosyl-transferase [APRT] and dihydroorotate dehydrogenase [DHODH]) were collected and then ADMET and PASS analyses were conducted using the Lipinski rule and Veber's rule. Additionally, molecular docking between screened ligands and proteins were performed. The stability of complexes was analyzed using molecular dynamics (MD) simulations and MMPBSA analysis. Initially, 6,220 unique molecules were collected from the PubChem database, and then the Lipinski rule and Veber's rule were used for screening. In total, 203 compounds passed the ADMET test; their antileishmanial properties were tested by PASS analysis. As a result, 15 ligands were identified. Molecular docking simulations between APRT or DHODH and these 15 ligands were performed. Four molecules were found to be plant-derived compounds. Lig_2 and Lig_3 had good docking scores with both proteins. MD simulations were performed to determine the dynamic behavior and binding patterns of complexes. Both MD simulations and MMPBSA analysis showed Lig_3 is a promising antileishmanial inhibitor of both targets. Promising plant-derived compounds that might be used to combat VL were obtained through a multi-target approach.

Rapid detection of traditional Chinese medicine with neuraminidase inhibitory activities based on high-throughput and virtual screening strategy

BackgroundOseltamivir, a neuraminidase inhibitor (NAI), is the primary and first-line anti-influenza drug. In recent years, more and more oseltamivir resistant strains appeared frequently. PurposeTo identify anti-influenza candidates to overcome oseltamivir resistance from traditional Chinese medicine. MethodsHigh-throughput screening platform was used to screen candidates with oseltamivir sensitive and resistant neuraminidase (NA) inhibitory activities from traditional Chinese medicine (TCM) and in validation of potential active components in vitro. Molecular docking is used for virtual screening of TCM compound libraries and analysis of the molecular mechanism of active compounds. ResultsSix out of 188 TCM formula granules were screened out with good inhibitory activities in oseltamivir sensitive (H5N1) and resistant NA (H274Y mutant). A compound library containing 679 candidates in the above six plants were docked into binding pockets of H5N1 NA and its H274Y mutant. The results indicated that diverse structural types, including flavonoids glycosides, alkaloids, caffeoylquinic acid derivatives, etc. showed good docking scores on the two NAs. Furthermore, 10 representative compounds tested in vitro showed inhibitory activities in both oseltamivir sensitive and resistant NA. The docking simulations revealed that natural TCM molecules bind with NA in an absolute different mode compared with oseltamivir, which occupy the extra cavities adjacent to the active site of NA, thus might make them non-susceptible to be influenced by mutation around the active sites. ConclusionsThe combination of high-throughput screening and molecular docking can efficiently screen out candidates that have the potential to overcome oseltamivir resistance from TCM.

Evaluation of Mollugo oppositifolia Linn. as cholinesterase and β-secretase enzymes inhibitor.

Mollugo oppositifolia Linn. is traditionally used in neurological complications. The study aimed to investigate in-vitro neuroprotective effect of the plant extracts through testing against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase linked to Alzheimer's disease (AD). To understand the safety aspects, the extracts were tested for CYP450 isozymes and human hepatocellular carcinoma cell (HepG2) inhibitory potential. The heavy metal contents were estimated using atomic absorption spectroscopy (AAS). Further, the antioxidant capacities as well as total phenolic content and total flavonoid content (TFC) were measured spectrophotometrically. UPLC-QTOF-MS/MS analysis was employed to identify phytometabolites present in the extract. The interactions of the ligands with the target proteins (AChE, BChE, and BACE-1) were studied using AutoDockTools 1.5.6. The results showed that M. oppositifolia extract has more selectivity towards BChE (IC50 = 278.23 ± 1.89μg/ml) as compared to AChE (IC50 = 322.87 ± 2.05μg/ml). The IC50 value against β-secretase was 173.93μg/ml. The extract showed a CC50 value of 965.45 ± 3.07μg/ml against HepG2 cells and the AAS analysis showed traces of lead 0.02 ± 0.001 which was found to be within the WHO prescribed limits. Moreover, the IC50 values against CYP3A4 (477.03 ± 2.01μg/ml) and CYP2D6 (249.65 ± 2.46μg/ml) isozymes justify the safety aspects of the extract. The in silico molecular docking analysis of the target enzymes showed that the compound menthoside was found to be the most stable and showed a good docking score among all the identified metabolites. Keeping in mind the multi-targeted drug approach, the present findings suggested that M. oppositifolia extract have anti-Alzheimer's potential.

HR-LCMS assisted phytochemical screening of antioxidant, antibacterial activity of Priva cordifolia (L.f) Druce plant and molecular docking approach

Ethnomedicinal plants have been employed for treatments in phytotherapy due to the quality, effectiveness, and assurance of herbal therapy. The present study aims to assess the different extracts (16 extracts) obtained from foliage, stem bark, root, and seeds by increased polarity solvent-based on extraction and analyze the antioxidant properties of Priva cordifolia (L.f) Druce plant. Total polyphenols and flavonoids have been found to range from 20.60 ± 0.19–148.20 ± 1.52 mg/g as gallic acid equivalent (GAE) and 7.31 ± 0.09–350.46 ± 12.80 mg/g as rutin equivalent (RE) respectively. All the extracts have been assessed for DPPH, ABTS scavenging radical and FRAP activity. Among these, methanol and acetone extract of the foliage showed excellent activity. The foliage extract was further fractioned and examined for antioxidant and antibacterial activity. A total of 27 metabolites were identified with the help of HRLC-MS. All the identified metabolites were tested for pharmacophore model, ADME, Blood-Brain Barrier, and Molecular docking analysis. In this insilico method, all compounds have given a good docking score and binding energy to the particular protein target, which ranges from − 6 to −10 against DNA gyrase protein (3G7B).The fraction was further evaluated for their cytotoxicity against normal cell L6 and revealed data showing insignificant toxicity. The foliage methanolic extract indicated a broad phytochemical in P. cordifolia and is yet to explore unknown vital constituents for the medicinal applications in the future.

Synthesis, characterization, biological evaluation and docking studies of novel 5-(2-methyl-1,8-naphthyridin-3-yl)-1,3,4-oxadiazol-2-amine and some of its derivatives using symmetrical anhydrides

The present work demonstrates the novel compounds of 5-(2-methyl-1,8-naphthyridin-3-yl)-1,3,4-oxadiazol-2-amine and its derivatives using symmetrical anhydrides. The synthesized 5-(2-methyl-1,8-naphthyridin-3-yl)-1,3,4-oxadiazol-2-amine and its derivatives were successfully characterized by 1H NMR, FTIR, 13C NMR, and Mass Spectral data. The synthesized compounds of formula 5 and 5(a-j) have been screened for their in-vitro antibacterial and antifungal properties against Staphylococcus aureus and Escherichia coli as bacterial strains and Candida albicans as a fungal strain. The antimicrobial activity was compared using reference compounds by disc diffusion method and the majority of the compounds exhibited significant antimicrobial activity, and some of them were exhibited promising antimicrobial activity. In addition, all the novel compounds have good docking scores.

Molecular docking and dynamic simulation studies of terpenoid compounds against phosphatidylinositol-specific phospholipase C from Listeria monocytogenes

Listeriosis has emerged to be one of the life-threatening foodborne diseases worldwide, especially for immunocompromised individuals. The aim of this study was to develop a potential anti-bacterial drug with plant phytocompounds against phosphatidylinositol-specific phospholipase C from Listeria monocytogenes. A series of forty terpenoid compounds were selected based on Lipinski's rule of 5 and were subjected to molecular docking and dynamic simulation studies. From the results, Vouacapan was identified to be the promising compound out of the forty terpenoid compounds as it exhibited a good docking score of −7.7 kcal/mol and better stability with the protein in 100ns MD trajectory. Using MM/GBSA method, a total binding free energy value of −14.25 kcal/mol was observed for the Vouacapan-protein complex. The study offers a molecular level understanding of interactions of the selected compounds against the virulent protein.

Response Surface Methodology (RSM) Approach for Optimization of Parameters for Synthesis of Organic Compounds and Evaluation of Biological Activity with Molecular Docking

The triazolidine derivatives were synthesized by green and sustainable chemistry approach. The response surface methodology (RSM) was applied to optimize the reaction parameters during the synthesis. Reaction parameter which affect the yield of product were studied, which includes the temperature and time of the reaction. Various statistical RSM with different central composite designs (CCD) such as circumscribed (CCC), face-centered (CCF) and inscribed (CCI) were used to find the maximum yield of the product (%) of reaction at the given parameters and selected, which gave the maximum possible yield. The relationship between reaction parameters (temperature and time) and the yield of product modeled using second-order response surface model. The optimum reaction parameters given by CCI were 80.8 ºC reaction temperature and 15.03 min reaction time with yield of product is up to 94.57%. The adequacy and reliability of the predicted model was checked by ANOVA, R-square and adjusted R-square and revealed the good agreement between predicted model and actual experimental data. The study described here can be efficiently applied for the optimization of parameters in the synthesis of any organic compound. The molecular docking was carried out by using AutoDock vina 1.2.0 on (CYP51) [PDBID: 1EA1] and (DprE1) [PDBID: 4FDO] for target anti-tuberculosis activity while (FabH) [PDBID: 1HNJ] for target antimicrobial activity. There was better interaction within receptor amino acids compound 3d and 3b with FabH and CYP51 enzyme, respectively for anti-tuberculosis activity and compound 3d with DprE1 enzyme for antimicrobial activity observed very good docking score among all compounds.

Bioactive Phytoconstituents of Leucas zeylanica and its Molecular Docking Study

Bioactive phytoconstituents 1-3 were isolated from the chloroform extract of aerial parts of Leucas zeylanica. Structure of all the three compounds were elucidated by the spectroscopic analysis data. Three compounds showed good activities, but compound 2 exhibited significant in vitro antioxidant activity. In molecular docking study of compound 2 also showed good docking score within binding pocket of the selected proteins.

Computer-Aided Drug Designing of Ocimum basilicum Compounds as Therapeutic Agents against RdRp of SARS-CoV2

The prevailing situation of the World is challenging due to COVID-19 pandemic that is caused by SARS-CoV2. Objectives: To combat with this emerging pandemic by reducing disease severity and infection, the need of hour is to develop an effective vaccine and antiviral candidates as therapeutic agents against SARS-CoV2. Methods: This study was developed for the identification of potential anti-viral agents, from Ocimum basilicum against RdRp of SARS-CoV2. In this concern, nevadensin, ursolic acid, β-Sesquiphellandren, apigenin, nerolidol, nonyl acetate and geranyl acetate were screened out of fifty-seven compounds from Ocimum basilicum based on their best docking scores. The docking results were also compared with already clinically used drugs (Remdesivir and Ribavirin) against the RdRp of SARS-CoV2. Molecular docking was performed using MOE software. The ADMET analysis and drug likeliness were also performed for all screened compounds by using admetSAR, pkCSM and SwissADME. Results: Cumulatively, the optimum binding energies of screened compounds indicated their potential for drug development against SARS-CoV2. It appears promising that nevadensin exhibited a good docking score and high binding affinity towards RdRp of SARS-CoV2. Therefore, it may represent the potential to inhibit COVID-19. Conclusion: Hence, Ocimum basilicum nutraceuticals could be effective therapeutic candidates for the treatment and prevention of COVID-19.

Design, Synthesis, Characterization of Novel Sulfathiazole Derivatives and their in silico and in vitro Analysis against Multidrug-Resistance Tuberculosis using Docking Studies

In this study, seven novel sulfathiazole derivatives were synthesized from sulfathiazole using different substituted aldehydes and characterized by IR, NMR and LC-MS analysis. Using molecular docking and toxicity prediction, all the seven novel sulfathiazole derivatives (Mol-14, Mol-15, Mol-21, Mol-27, Mol-36, Mol-39 and Mol-43) were virtually screened from generated 70 compounds and assessed their effectiveness against multidrug resistant Mycobacterium tuberculosis (MDR-TB). The Inha protein of TB were performed and all the compounds found to have good docking scores in the range of -7.2 to -9.1 Kcal/mol. Compound, 4-(4-oxo-2-phenyl-1,3-thiazolidin-3-yl)-N-(1,3-thiazol-2-yl)benzene-1- sulfonamide (Mol-27) shown to inhibit the MDR-TB and wild-type TB strain with an MIC value of 1 μg/mL and 0.25, respectively. The standard sulfathiazole and isoniazid were compared to the minimal inhibitory concentration (MIC) of the synthesized Mol-14, Mol-15, Mol-21, Mol-27, Mol-36, Mol-39 and Mol-43 new sulfathiazole derivatives. Based on the results, these compounds shows promising activity against MDR-TB.

Organotin Antifouling Compounds and Sex-Steroid Nuclear Receptor Perturbation: Some Structural Insights.

Organotin compounds (OTCs) are a commercially important group of organometallic compounds of tin used globally as polyvinyl chloride stabilizers and marine antifouling biocides. Worldwide use of OTCs has resulted in their ubiquitous presence in ecosystems across all the continents. OTCs have metabolic and endocrine disrupting effects in marine and terrestrial organisms. Thus, harmful OTCs (tributyltin) have been banned by the International Convention on the Control of Harmful Antifouling Systems since 2008. However, continued manufacturing by non-member countries poses a substantial risk for animal and human health. In this study, structural binding of common commercial OTCs, tributyltin (TBT), dibutyltin (DBT), monobutyltin (MBT), triphenyltin (TPT), diphenyltin (DPT), monophenyltin (MPT), and azocyclotin (ACT) against sex-steroid nuclear receptors, androgen receptor (AR), and estrogen receptors (ERα, ERβ) was performed using molecular docking and MD simulation. TBT, DBT, DPT, and MPT bound deep within the binding sites of AR, ERα, and Erβ, showing good dock score, binding energy and dissociation constants that were comparable to bound native ligands, testosterone and estradiol. The stability of docking complex was shown by MD simulation of organotin/receptor complex with RMSD, RMSF, Rg, and SASA plots showing stable interaction, low deviation, and compactness of the complex. A high commonality (50-100%) of interacting residues of ERα and ERβ for the docked ligands and bound native ligand (estradiol) indicated that the organotin compounds bound in the same binding site of the receptor as the native ligand. The results suggested that organotins may interfere with the natural steroid/receptor binding and perturb steroid signaling.

Identification of phytochemicals from Tundub Capparis decidua (Forssk) Edgew seed oil as potential anticancer agents using gas chromatography-mass spectroscopy analysis, molecular docking, and molecular dynamics studies

Natural products are an important source of anticancer agents. Early efforts to find anticancer therapies from natural products have largely focused on molecules with cytotoxicity potential. Capparis decidua is a plant with economic, nutritional, and pharmaceutical importance. The purpose of this study was to study phytochemical aspects using gas chromatography-mass spectrometry (GC-MS) analysis and computational studies to evaluate the anticancer activity of C. decidua seed oil. GC-MS analysis of the oil revealed the presence of 26 compounds. The three main compounds were 11-Octadecenoic acid, methyl ester (25%), hexadecanoic acid, methyl ester (17.43%), 9-octadecenoic acid (Z)-, methyl ester (16.86%). Computational studies have shown that ten compounds have a good binding affinity for Mcl-1, a protein widely expressed in various cancer cells. These compounds have good docking scores with the highest values for the compounds CID530340, CID5284421, and CID8201. In addition, MM-GBSA binding free energy was in the range of −43.09 to −62.2 kcal/mol. These compounds showed acceptable lipophilicity (QPlogPo/w), high water solubility (QPlogS), excellent cell permeability (QPPMDCK and QPPCaco), good CNS penetration (QPlogBB), and excellent oral absorption. Furthermore, the stability of the three best compounds was investigated using molecular dynamics simulations over 100 ns. Finally, C. decidua oil is rich in unsaturated fatty acids with established molecular evidence supporting its anticancer potential.

Design and synthesis of novel substituted pyrazole as small molecule inhibitor of cytochrome P450 CYP121A1

Discovering new drugs with novel targets is vital for the success of treatment of tuberculosis as antibiotic resistance is increasing among the TB population. Mycobacterium tuberculosis cytochrome P450 CYP121A1 is a promising drug target for the treatment of tuberculosis owing to its essential role in mycobacterium growth. Using a rational approach, that includes molecular docking studies of some substituted pyrazole derivatives a series of pyrazole analogue were designed and pass through computational studies. Compound with good docking score and ADME profile were synthesized using two step reaction and biologically evaluated for their inhibitory activity towards M. tuberculosis. All compounds were analyzed by IR, LCMS, 1H NMR and 13C NMR. Among them 3 compounds shows significant activity having MIC (6.25 µg/ml).

Repurposing Thalidomide, its Analogue and Apremilast for Possible Antiviral in Situation of Severe COVID Cytokine Syndrome.

COVID-19, caused by SARS-corona virus-2, is a globally expanded public health risk at a bizarre level. In this current situation, COVID-19 has become a serious emerging pandemic. Drug reusing is a crucial step in identifying the new uses of old established drugs. To achieve a significant and healthy way of treatment in COVID patients within a short duration, drug repurposing is a novel method. The present study concentrated on the molecular docking of thalidomide and its analogues and Apremilast against Coronavirus infectious symptoms, and evaluated virus proteins (Spike Protein, 3cl Protease, Nucleocapsids). The present study explores the possibility of repurposing thalidomide for the treatment of SARS-COV-2 infection by assessing and confirming with docking affinity scores of thalidomide and its analogues and Apremilast, with spike protein, 3cl protease, and nucleocapsids. From the study results, thalidomide, pomalidomide, lenalidomide, and Apremilast exhibited better binding affinity to N Protein (4KXJ), Protease (4WY3) and Spike Protein (5WRG). In comparison to targets, N Protein - 4KXJ is the best for the four ligands. It is finalized that all four ligands (Thalidomide -8.6, Pomalidomide -8.8, Lenalidomide, and -8.2,and Apremilast -8.1) have good docking scores with the target N Protein. The present study confirms that thalidomide and its analogues and apremilast are a better fit for treating high risk patients of COVID-19 viral infection, which are supposed to promote beneficial effects for both respiratory illnesses like COVID-19 symptoms as well as improve the pathological state of condition.

Novel Gatifloxacin3-Carboxamide Derivatives as Anti-Tumor Agents: Synthesis, Enantioseparation, and Molecular Docking

Background:: The drug's affinity to the identified target (protein/enzyme) is a critical characteristic in the development of a novel drug. Fluoroquinolone derivatives with a carboxylic group change have improved antimicrobial and anticancer activity while maintaining antibacterial activity similar to parent drugs. Aim:: The rationale upon which synthesis of the new compounds, evaluation of their anticancer activity with in silico study, and suggestion of their mechanism of action is presented in this paper. Methods:: This part describes the practical procedures used for the synthesis of four new gatifloxacin 3-carboxamide derivative, with their spectral data (UV-vis, IR, and 1H-NMR). The enantiosaparation and docking studies are presented and discussed. Results:: Four gatifloxacin 3-carboxamide derivatives were enantioseparated using a high-performance liquid chromatography approach using two distinct polysaccharide-based chiral stationary phases (CSPs). The baseline enantioseparation of all derivatives evaluated in this study was achieved using both coated and immobilized amylose columns. In silico molecular docking study, revealed that all compounds showed good docking score. Conclusion:: The novel Fluoroquinolone caboxamides derivatives could be repositioned as DNA topoisomerase II inhibitors, allowing them to be employed as anticancer agents, according to our in silico study. Experiments in vitro and in vivo are required to confirm their efficacy.

MOLECULAR DOCKING STUDY OF COMPOUND ISOLATED FROM COCCINIA GRANDIS (L.) VOIGT

Compound (9Z, 12Z)-octadeca-9, 12-dienoic acid (CGHY 02) was isolated from Coccinia grandis (L.) Voigt n-butanol extract by column chromatography. A molecular docking study against human pancreatic alpha-amylase enzyme (PDB: 3OLE) yielded a good docking score of -112.37 Kcal mol-1, indicating a high affinity of the compound to the receptor via hydrogen bonds, electrostatic interactions and hydrophobic interactions. The hydrogen bond was observed between the hydroxyl group of the compound and glutamine 8, whereas the carbonyl group and C5-C9 chain of the compound revealed steric interactions with glutamine 8 and aspartate 402, respectively. In vitro alpha-amylase inhibition of (CGHY 02) demonstrated remarkable inhibition (68.47 %) at low concentration (100 µL mL-1) compared to standard acarbose. Moreover, in silico ADME analysis of the compound exhibited 92.282 % gastrointestinal absorption, skin permeability, activity as a substrate for CYP2D6 and CYP3A4 enzymes resulting in better metabolism and 1.936 (logn ml min-1 kg-1) of total clearance of the compound. In silico toxicity predicted carcinogenicity, mutagenicity via PreADMET online server and hepatotoxicity and skin irritations via pkCSM online platforms. Antidiabetic potential of (CGHY 02) is attributed through inhibition of human pancreatic alpha amylase enzyme.

Synthesis, characterization and molecular docking studies of highly functionalized and biologically active derivatives of 2-aminothiazole

Many derivatives of 2-aminothiazoles are found to have significant biological properties and used as potential antibacterial and antifungal drugs. Therefore new synthetic methodologies for deriving 2-aminothiazole scaffolds are enabled in order to develop enhanced drug activity and therapeutic properties. In this study, a new series of 2-aminothiazole derivatives are synthesized via the cyclocondensation reaction of thiourea with appropriate acid halides followed by condensation with highly functionalized amines to get the amides of biological interest. The products thus obtained are characterized by IR, 1H NMR, 13C NMR and mass spectral data. The synthesized 2-aminothiazole derivatives were screened for antibacterial activity against Bacillus cereus bacterial strains using serial broth dilution methods. In addition the 2-aminothiazole derivatives are screened for their in vitro anti-bacterial and anti-fungal activity through microbial incubatory concentration (MIC) and molecular docking. This in silico technique is used to identify the interaction modes of the derived products with the active site of foodborne pathogen Bacillus cereus and yeast form of fungal pathogen Candida albicans. The study shows good docking scores with acceptable binding interactions.

Aspartate α-decarboxylase a new therapeutic target in the fight against Helicobacter pylori infection.

Effective eradication therapy for Helicobacter pylori is a worldwide demand. Aspartate α-decarboxylase (ADC) was reported as a drug target in H. pylori, in an in silico study, with malonic acid (MA) as its inhibitor. We evaluated eradicating H. pylori infection through ADC inhibition and the possibility of resistance development. MA binding to ADC was modeled via molecular docking. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of MA were determined against H. pylori ATCC 43504, and a clinical H. pylori isolate. To confirm selective ADC inhibition, we redetermined the MIC in the presence of products of the inhibited enzymatic pathway: β-alanine and pantothenate. HPLC was used to assay the enzymatic activity of H. pylori 6x-his tagged ADC in the presence of different MA concentrations. H. pylori strains were serially exposed to MA for 14 passages, and the MICs were determined. Cytotoxicity in different cell lines was tested. The efficiency of ADC inhibition in treating H. pylori infections was evaluated using a Sprague-Dawley (SD) rat infection model. MA spectrum of activity was determined in different pathogens. MA binds to H. pylori ADC active site with a good docking score. The MIC of MA against H. pylori ranged from 0.5 to 0.75 mg/mL with MBC of 1.5 mg/mL. Increasing β-alanine and pantothenate concentrations proportionally increased MA MIC. The 6x-his tagged ADC activity decreased by increasing MA concentration. No resistance to ADC inhibition was recorded after 14 passages; MA lacked cytotoxicity in all tested cell lines. ADC inhibition effectively eradicated H. pylori infection in SD rats. MA had MIC between 0.625 to 1.25 mg/mL against the tested bacterial pathogens. In conclusion, ADC is a promising target for effectively eradicating H. pylori infection that is not affected by resistance development, besides being of broad-spectrum presence in different pathogens. MA provides a lead molecule for the development of an anti-helicobacter ADC inhibitor. This provides hope for saving the lives of those at high risk of infection with the carcinogenic H. pylori.