Molecular docking analysis of known flavonoids as duel COX-2 inhibitors in the context of cancer

Cyclooxygenase-2 (COX-2) catalyzed synthesis of prostaglandin E2 and it associates with tumor growth, infiltration, and metastasis in preclinical experiments. Known inhibitors against COX-2 exhibit toxicity. Therefore, it is of interest to screen natural compounds like flavanoids against COX-2. Molecular docking using 12 known flavanoids against COX-2 by FlexX and of ArgusLab were performed. All compounds showed a favourable binding energy of >-10 KJ/mol in FlexX and > -8 kcal/mol in ArgusLab. However, this data requires in vitro and in vivo verification for further consideration.     

Computer aided screening of natural compounds targeting the E6 protein of HPV using molecular docking

The cancer profile in the Indian state of Uttarakhand reveals that the breast cancer is the most prevalent type of cancers in females followed by cervical and ovarian type. Literature survey shows that the E6 protein of Human Papilloma Virus-16 (HPV-16) is responsible for causing several forms of cancer in human. Therefore, it is of interest to screen HPV-16 E6 target protein with known natural compounds using computer aided molecular modeling and docking tools. The complete structure of E6 is unknown. Hence, the E6 structure model was constructed using different online servers followed by molecular docking of Colchine, Curcumin, Daphnoretin, Ellipticine and Epigallocatechin-3-gallate; five known natural compounds with best E6 protein model predicted by Phyre2 server. The screening exercise shows that Daphnoretin (with binding free energy of -8.3 kcal/mol), a natural compound derived from Wikstroemia indica has the top binding properties. Thus, it is of interest to consider the compound for further validation.     

A Homology Based Model and Virtual Screening of Inhibitors for Human Geranylgeranyl Transferase 1 (GGTase1)

Protein prenylation is a post translational modification that is indispensable for Ras–Rho mediated tumorigenesis. In mammals, three enzymes namely protein farnesyltransferase (FTase), geranylgeranyl transferase1 (GGTase1), and geranylgeranyl transferase2 (GGTase2) were found to be involved in this process. Usually proteins of Ras family will be farnesylated by FTase, Rho family will be geranylgeranylated by GGTase1. GGTase2 is exclusive for geranylgeranylating Rab protein family. FTase inhibitors such as FTI- 277 are potent anti-cancer agents in vitro. In vivo, mutated Ras proteins can either improve their affinity for FTase active site or undergo geranylgeranylation which confers resistance and no activity of FTase inhibitors. This led to the development of GGTase1 inhibitors. A well-defined 3-D structure of human GGTase1 protein is lacking which impairs its in silico and rational designing of inhibitors. A 3-D structure of human GGTase1 was constructed based on primary sequence available and homology modeling to which pubchem molecules library was virtually screened through AutoDock Vina. Our studies show that natural compounds Camptothecin (-8.2 Kcal/mol), Curcumin (-7.3 Kcal/mol) have higher binding affinities to GGTase-1 than that of established peptidomimetic GGTase-1 inhibitors such as GGTI-297 (-7.5 Kcal/mol), GGTI-298 (-7.5 Kcal/mol), CHEMBL525185 (-7.2 Kcal/mol).     

Structure based molecular inhibition of Caspase-8 for treatment of multi-neurodegenerative diseases using known natural compounds

Neurodegenerative disorders are often associated with excessive neuronal apoptosis. It is well known that apoptosis is regulated by some intracellular proteases, such as, Caspases (cysteine-dependent, aspartate-specific proteases). In fact, Caspase-8 which is an initiator caspase, has been identified as a key mediator of neuronal apoptosis. In addition, Caspase-8 is found to be coupled with the regulation of various neurodegenerative disorders including Alzheimer׳s disease (AD), Parkinson׳s disease (PD), Huntington׳s Diseases (HD) and Dentatorubral Pallidoluysian Atrophy (DRPLA). Caspase-8 inhibition may provide an effective means of treatment for multiple neurodegenerative disorders. Therefore, the present study describes the molecular interaction of some selected natural compounds with known anti neurodegenerative properties with Caspase-8. Docking between Caspase-8 and each of these compounds (separately) was performed using ‘Autodock4.2’. Out of all the selected compounds, rosmarinic acid and curcumin proved to be the most potent inhibitors of Caspase-8 with binding energy (ΔG) of -7.10 Kcal/mol and -7.08 Kcal/mol, respectively. However, further in vitro and in vivo studies are needed to validate the anti-neurodegenerative potential of these compounds.     

Molecular docking analysis of COX-2 with compounds from Piper longum

Piper longum (Indian long pepper) is known for its use as an anti inflammatory agent in Indian Ayurvedic System of medicine. Therefore, it is of interest to document the molecular docking analysis of compounds from Piper longum with COX-2 using the Autodock Vina PyRx tool. Molecular docking results show that asarinine, sesamine, fargesin, and piperlonguminine have optimal binding energy of 10, 10, -9.5 and 9.4 Kcal/mol, respectively for further consideration.     

Larvicidal activity of novel anthraquinone analogues and their molecular docking studies

To investigate the larvicidal activities of novel anthraquinones (1a-1k) against Culex quinquefasciatus mosquito larvae. Novel anthraquinones (1a-1k) derivatives were synthesis via condensation method. The compounds were confirmed through FT-IR spectroscopy, ¹H & ¹³C NMR spectrum, and mass spectral studies. The larvicidal activity of compound 1c was highly active LD₅₀ 20.92 µg/mL against Culex quinquefasciatus compared standard permethrin with LD₅₀ 25.49 µg/mL. Molecular docking studies were carried out for compound 1c against Odorant-binding protein of Culex quinquefasciatus. The compound 1c (−9.8 Kcal/mol) was a potent larvicide with more binding energy than control permethrin (−9.7 Kcal/mol). Therefore, compound (1c) may be more significant inhibitors of mosquito larvicidal.     

Investigation of SARS-CoV-2 Main Protease Potential Inhibitory Activities of Some Natural Antiviral Compounds Via Molecular Docking and Dynamics Approaches

Coronaviruses caused an outbreak pandemic disease characterized by a severe acute respiratory distress syndrome leading to the infection of more than 200 million patients and the death of more than 4 million individuals. The primary treatment is either supportive or symptomatic. Natural products have an important role in the development of various drugs. Thus, screening of natural compounds with reported antiviral activities can lead to the discovery of potential inhibitory entities against coronaviruses. In the current study, an in-silico molecular docking experiment was conducted on the effects of some of these natural antiviral phytoconstituents, (e.g., procyanidin B2, theaflavin, quercetin, ellagic acid, caffeoylquinic acid derivatives, berginin, eudesm-1β, 6α, 11-triol and arbutin), on the crystal structure of SARS-CoV-2 main protease (PDB ID: 6w63) using AutoDock-Vina software. Many of the docked compounds revealed good binding affinity, with procyanidin B2 (–8.6 Kcal/mol) and theaflavin (–8.5 Kcal/mol) showing a better or similar binding score as the ligand (–8.5 Kcal/mol). Molecular dynamics simulations were carried out at 100 ns and revealed that procyanidin B2 forms a more stable complex with SARS-CoV-2 main protease than theaflavin. Procyanidin B2, theaflavin, and 4,5-dicaffeoylquinic acid were evaluated for toxicity by ProTox-II webserver and were non-toxic according to the predicted LD50 values and safe on different organs and pathways. Additionally, these phytoconstituents showed good ADME properties and acceptable lipophilicity, as evaluated using WLOGP. Amongst the tested compounds, procyanidin B2 showed the highest lipophilic value. It is worth mentioning that these natural inhibitiors of SARS-CoV-2 main protease are components of green and black tea that can be used as a supporting supplement for COVID patients or as potential nuclei for further drug design and development campaigns.     

Structure based prediction of functional sites with potential inhibitors to Nudix enzymes from disease causing microbes

The functional sites were predicted for Nudix enzymes from pathogenic microorganisms such as Streprococcus pneumonia (2B06) and Enterococcus faecalis (2AZW). Their structures are already determined, however, no data is reported about their functional sites, substrates and inhibitors. Therefore, we report prediction of functional sites in these Nudix enzymes via Geometric Invariant (GI) technique (Construct different geometries of peptides which remain unchanged). The GI method enumerated 2B06: RA57, EA58, EA61, EA62 and 2AZW: RA62, EA63, EA66, EA67 as putative functional sites in these Nudix enzymes. In addition, the substrate was predicted via Molecular docking (Docking of substrates against whole structure of Nudix enzymes). The substrate ADP-Ribose was docked with the Nudix enzymes, 2B06 (Docking energy -15.68 Kcal/mol) and 2AZW (Docking energy -10.86 Kcal/mol) with the higher affinity and the lower docking energy as compared to other substrates. The residues EA62 in 2B06 and RA62 in 2AZW make hydrogen bonds with the ADP-ribose. Furthermore, we screened 51 inhibitor compounds against structures of 2B06 and 2AZW. The inhibitor compounds AMPCPR and CID14258187 were docked well as compared to other compounds. The compound CID14258187 was also in agreement with Lipinski rule of 5 for drug likeness properties. Therefore, our findings of functional sites, substrates and inhibitors for these Nudix enzymes may help in structure based drug designing against Streprococcus pneumonia and Enterococcus faecalis.     

Virtual screening and pharmacophore studies for ftase inhibitors using Indian plant anticancer compounds database

Farnesyl transferase (FTase) is an enzyme responsible for post-translational modification in proteins having a carboxy-terminal CaaX motif in human. It catalyzes the attachment of a lipid group in proteins of RAS superfamily, which is essential in signal transduction. FTase has been recognized as an important target for anti cancer therapeutics. In this work, we performed virtual screening against FTase with entire 125 compounds from Indian Plant Anticancer Database using AutoDock 3.0.5 software. All compounds were docked within binding pocket containing Lys164, Tyr300, His248 and Tyr361 residues in crystal structure of FTase. These complexes were ranked according to their docking score, using methodology that was shown to achieve maximum accuracy. Finally we got three potent compounds with the best Autodock docking Score (Vinorelbine: -21.28 Kcal/mol, Vincristine: -21.74 Kcal/mol and Vinblastine: -22.14 Kcal/mol) and their energy scores were better than the FTase bound co-crystallized ligand (L- 739: -7.9 kcal/mol). These three compounds belong to Vinca alkaloids were analyzed through Python Molecular Viewer for their interaction studies. It predicted similar orientation and binding modes for these compounds with L-739 in FTase.Thus from the complex scoring and binding ability it is concluded that these Vinca alkaloids could be promising inhibitors for FTase. A 2-D pharmacophore was generated for these alkaloids using LigandScout to confirm it. A shared feature pharmacophore was also constructed that shows four common features (one hydogen bond Donar, Two hydrogen bond Acceptor and one ionizable area) help compounds to interact with this enzyme.     

Docking of oxalyl aryl amino benzoic acid derivatives into PTP1B

Protein Tyrosine Phosphatases (PTPs) that function as negative regulators of the insulin signaling cascade have been identified as novel targets for the therapeutic enhancement of insulin action in insulin resistant disease states. Reducing Protein Tyrosine Phosphatase1B (PTP1B) abundance not only enhances insulin sensitivity and improves glucose metabolism but also protects against obesity induced by high fat feeding. PTP1B inhibitors such as Formylchromone derivatives, 1, 2-Naphthoquinone derivatives and Oxalyl aryl amino benzoic derivatives may eventually find an important clinical role as insulin sensitizers in the management of Type-II Diabetes and metabolic syndrome. We have carried out docking of modified oxalyl aryl amino benzoic acid derivatives into three dimensional structure of PTP1B using BioMed CAChe 6.1. These compounds exhibit good selectivity for PTP1B over most of phosphatases in selectivity panel such as SHP-2, LAR, CD45 and TCPTP found in literature. This series of compounds identified the amino acid residues such as Gly220 and Arg221 are important for achieving specificity via H-bonding interactions. Lipophilic side chain of methionine in modified oxalyl aryl amino benzoic acid derivative [1b (a2, b2, c1, d)] lies in closer vicinity of hydrophobic region of protein consisted of Meth258 and Phe52 in comparison to active ligand. Docking Score in [1b (a2, b2, c1, d)] is -131.740Kcal/mol much better than active ligand score -98.584Kcal/mol. This information can be exploited to design PTP1B specific inhibitors.     

Anti-methanogenic effect of rhubarb (Rheum spp.) – An in silico docking studies on methyl-coenzyme M reductase (MCR)

The present study explored anti-methanogenic properties of rhubarb compounds using in silico analysis on methyl-coenzyme M reductase (MCR) for identifying its anti-methanogen mechanism. To identify pharmacokinetics of 35 compounds from rhubarb, molecular docking and ADME analysis were performed against MCR using AutoDockVina, FAFDrugs3 and PROTOX programs. Docking results successfully indicated three possible candidate compounds 9,10-anthracenedione, 1,8-dihydroxy-3-methyl (?6.92 kcal/mol); phthalic acid isobutyl octadecyl ester (?5.26 kcal/mol); and diisooctyl phthalate (?5.61 kcal/mol) showed minimum binding energy (kcal/mol) with the target protein MCR which catalyze the biosynthesis of rumen methane. In conclusion, the identified compounds showed the most docking fitness score against the target methyl-coenzyme M reductase and the decrease in ruminal methane emission by rhubarb might be a result of these compounds by inhibition of methanogenesis.     

In silico identification and study of potential anti-mosquito juvenile hormone binding protein (MJHBP) compounds as candidates for dengue virus - Vector insecticides

Dengue has become a huge global health burden. It is currently recognized as the most rapidly spreading mosquito-borne viral disease. Yet, there are currently no licensed vaccines or specific therapeutics to manage the virus, thus, scaling up vector control approaches is important in controlling this viral spread. This study aimed to identify and study in silico, potential anti-mosquito compounds targeting Juvenile hormone (JH) mediated pathways via the Mosquito Juvenile Hormone Binding Protein (MJHBP). The study was implemented using series of computational methods. The query compounds included pyrethroids and those derived from ZINC and ANPDB databases using a simple pharmacophore model in Molecular Operating Environment (MOE). Molecular docking of selected compounds’ library was implemented in MOE. The resultant high-score compounds were further validated by molecular dynamics simulation via Maestro 12.3 module and the respective Prime/Molecular Mechanics Generalized Born Surface Area (Prime/MM-GBSA) binding energies computed. The study identified compounds-pyrethroids, natural and synthetic - with high docking energy scores (ranging from 10.91–12.34 kcal/mol). On further analysis of the high-ranking (in terms of docking scores) compounds using MD simulation, the compounds - Ekeberin D4, Maesanin, Silafluofen and ZINC16919139- revealed very low binding energies (?122.99, ?72.91 -104.50 and,-74.94 kcal/mol respectively), fairly stable complex and interesting interaction with JH-binding site amino acid residues on MJHBP. Further studies can explore these compounds in vitro/in vivo in the search for more efficient mosquito vector control.     

Screening and design of anti-diabetic compounds sourced from the leaves of neem (Azadirachta indica)

Diabetes Mellitus is affecting people of all age groups worldwide. Many synthetic medicines available for type 2 diabetes mellitus in the market. However, there is a strong requirement for the development of better anti-diabetes compounds sourced especially from natural sources like medicinal plants. The extracts from the leaves of neem (Azadirachta indica) is traditionally known to have anti-diabetes properties. Therefore, there is an increased interest to identify potential compounds identified from neem leaf extracts showing predicted binding property with the known diabetes mellitus type 2 protein enzyme target phosphoenol-pyruvate carboxykinase(PEPCK). The structure data for compounds found in the leaf extract of neem was screened against PEPCK using molecular docking simulation and screening techniques. Results show that the compound 3-Deacetyl-3-cinnamoyl-azadirachtin possesses best binding properties with PEPCK. This observation finds application for further consideration in in vitro and in vivo validation.     

Thiazolidinedione and thiazole derivatives potentiate norfloxacin activity against NorA efflux pump over expression in Staphylococcus aureus 1199B strains

Thiazol and thiazolidinedione derivatives are known in the literature for presenting several biological activities, such as anti-diabetic, anti-inflammatory, antiparasitic, antifungal and antimicrobial activity. With this in mind, this study reports on the synthesis and antibacterial activity of thiazole (NJ) and thiazolidinedione (NW) derivatives, as well as their effects in association with norfloxacin, against NorA efflux pumps in the Staphylococcus aureus 1199B (SA-1199B) strain. Among the 14 compounds evaluated, 9 were found to potentiate norfloxacin activity, with 4 compounds from the NJ series promoting a threefold norfloxacin MIC reduction. Molecular docking assays were used to confirm the binding mode of most active compounds. In the in silico study, the efficiency of the interaction of NJ series compounds with the NorA pump were evaluated. Derivatives from both series did not show considerable intrinsic antibacterial activity (MIC > 1024 μg/mL) against any of the tested strains. However, the NJ16 and NJ17 compounds, when associated with norfloxacin, reduced the MIC of this drug threefold and inhibited NorA pumps in the 1199B strain. Moreover, some NW (05, 10, 18, 19 and 21) and NJ compounds (16, 17, 18 and 20) presented low to moderate cytotoxicity against normal cells. Molecular docking studies supported the potent in vitro inhibitory activity of NJ16 and NJ17, which showed NJ16 and NJ17 possessed more favorable binding energies of −9.03 Kcal/mol and −9.34 Kcal/mol, respectively. In addition, NJ16 showed different types of interactions involved in complex stabilization. In conclusion, NJ16 and NJ17, in combination with norfloxacin, were able to completely restore the antibacterial activity of norfloxacin against S. aureus SA-1199B, the norA-overexpressing strain, with low cytotoxicity in normal cells.     

Potential natural mTOR inhibitors screened by in silico approach and suppress hepatic stellate cells activation

The mammalian target of rapamycin (mTOR), an atypical serine/threonine kinase, plays a central role in the regulation of cell proliferation, growth, differentiation, migration, and survival. In this study, the 3-D structure of the mTOR (PDB ID: 2FAP) was used for the docking of 47 natural compounds and compared with pharmacophore model of 14 known mTOR inhibitors to identify the novel and specific natural inhibitor. The top four compounds, rutin, curcumin, antroquinonol, and benzyl cinnamate, have been selected based on their PLP score and further validated with hepatic stellate cells NHSC and THSC. Curcumin and antroquinonol significantly inhibited NHSC and THSC cells proliferation in a dose-dependent manner, whereas rutin and benzyl cinnamate showed less alteration of cell viability. Rutin inhibited the phosphorylation of mTOR (p-mTOR) and p-p70 S6 K in NHSC and THSC cells by Western blotting. Additionally, p-p70 S6 K protein was significantly decreased by incubation with benzyl cinnamate and curcumin in THSC cells. Taken together, this result suggests that rutin is a potential mTOR inhibitor in screen hits of molecular docking to hamper the activation of HSC and further applications in the treatment of liver fibrosis.     

Biochemical evaluation and molecular docking assessment of Cymbopogon citratus as a natural source of acetylcholine esterase (AChE)- targeting insecticides

Acetylcholinesterase (AChE) has been an effective target for insecticide development which is a very important aspect of the global fight against insect-borne diseases. The drastic reduction in the sensitivity of insects to AChE-targeting insecticides like organophosphates and carbamates have increased the need for insecticides of natural origin. In this study, we used Drosophila melanogaster as a model to investigate the insecticidal and AChE inhibitory potentials of Cymbopogon citratus and its bioactive compounds. Flies were exposed to 100 and 200 mg/mL C. citratus leaf extract for a 3-h survival assay followed by 45 min exposure for negative geotaxis and biochemical assays. Molecular docking analysis of 45 bioactive compounds of the plant was conducted against Drosophila melanogaster AChE (DmAChE). Exposure to C. citratus significantly reduced the survival rate of flies throughout the exposure period and this was accompanied by a significant decrease in percentage negative geotaxis, AChE activity, catalase activity, total thiol level and a significant increase in glutathione-S-transferase (GST) activity. The bioactive compounds of C. citratus showed varying levels of binding affinities for the enzyme. (+)-Cymbodiacetal scored highest (?9.407 kcal/mol) followed by proximadiol (?8.253 kcal/mol), geranylacetone (?8.177 kcal/mol), and rutin (?8.148 kcal/mol). The four compounds occupied the same binding pocket and interacted with important active site amino acid residues as the co-crystallized ligand (1qon). These compounds could be responsible for the insecticidal and AChE inhibitory potentials of C. citratus and they could be further explored in the development of AChE-targeting insecticides.     

insilico Characterization and Homology Modeling of Arabitol Dehydrogenase (ArDH) from Candida albican

Background: Arabitol dehydrogenase (ArDH) is involved in the production of different sugar alcohols like arabitol, sorbitol, mannitol, erythritol and xylitol by using five carbon sugars as substrate. Arabinose, d-ribose, d-ribulose, xylose and d-xylulose are known substrate of this enzyme. ArDH is mainly produced by osmophilic fungi for the conversion of ribulose to arabitol under stress conditions. Recently this enzyme has been used by various industries for the production of pharmaceutically important sugar alcohols form cheap source than glucose. But the information at structure level as well as its binding energy analysis with different substrates was missing. Results: The present study was focused on sequence analysis, insilico characterization and substrate binding analysis of ArDH from a fungus specie candida albican. Sequence analysis and physicochemical properties showed that this protein is highly stable, negatively charged and having more hydrophilic regions, these properties made this enzyme to bind with number of five carbon sugars as substrate. The predicted 3D model will helpful for further structure based studies. Docking analysis provided free energies of binding of each substrate from a best pose as arabinose -9.8224calK/mol, dribose -11.3701Kcal/mol, d-ribulose -8.9230Kcal/mol, xylose -9.7007Kcal/mol and d-xylulose 9.7802Kcal/mol. Conclusion: Our study provided insight information of structure and interactions of ArDH with its substrate. These results obtained from this study clearly indicate that d-ribose is best substrate for ArDH for the production of sugar alcohols. This information will be helpful for better usage of this enzyme for hyper-production of sugar alcohols by different industries.     

Selection of herbal therapeutics against deltatoxin mediated Clostridial infections

Clostridium perfringens (a versatile pathogenic bacterium) secretes enterotoxins (the deltatoxin, virulent factor) and causes food borne gastroenteritis and gasgangrene. The organism was isolated and characterized from improperly cooked meat and poultry samples. The isolated organism showed multiple drug resistance indicating that the treatment is challenging. Hence, there is need for improved therapeutic agents. The rational design of improved therapeutics requires the crystal structure for the toxin. However, the structure for the toxin is not yet available in its native form. Thus, we modeled the toxin structure using α- hemolysin of Staphylococcus aureus (PDB: 3M4D chain A) as template. The docking of the toxin with the herbal extract curcumin (1,7-bis(4-hydroxy-3- methoxyphenyl)hepta-1,6-diene-3,5-dione) showed a binding energy of -8.6 Kcal/mol, in comparison to the known antibiotic Linezolid with binding energy of -6.1 Kcal/mol. This data finds application in the design and development of novel compounds against the deltatoxin from Clostridium perfringens.     

Computational aided mechanistic understanding of Camellia sinensis bioactive compounds against co-chaperone p23 as potential anticancer agent

Co-chaperon p23 has been well established as molecular chaperon for the heat shock protein 90 (Hsp90) that further leads to immorality in cancer cells by providing defense against Hsp90 inhibitors, and as stimulating agent for generating overexpressed antiapoptotic proteins, that is, Hsp70 and Hsp27. The natural compounds such as catechins from Camellia sinensis (green tea) are also well known for inhibition activity against various cancer. However, molecular interaction profile and potential lead bioactive compounds against co-chaperon p23 from green tea are not yet reported. To this context, we study the various secondary metabolites of green tea against co-chaperon p23 using structure-based virtual screening from Traditional Chinese Medicine (TCM) database. Following 26 compounds were obtained from TCM database and further studied for extra precision molecular docking that showed binding score between −10.221 and −2.276 kcal/mol with co-chaperon p23. However, relative docking score to known inhibitors, that is, ailanthone (−4.54 kcal/mol) and gedunin ( 3.60 kcal/mol) along with ADME profile analysis concluded epicatechin (−7.013 kcal/mol) and cis-theaspirone (−4.495 kcal/mol) as potential lead inhibitors from green tea against co-chaperone p23. Furthermore, molecular dynamics simulation and molecular mechanics generalized born surface area calculations validated that epicatechin and cis-theaspirone have significantly occupied the active region of co-chaperone p23 by hydrogen and hydrophobic interactions with various residues including most substantial amino acids, that is, Thr90, Ala94, and Lys95. Hence, these results supported the fact that green tea contained potential compounds with an ability to inhibit the cancer by disrupting the co-chaperon p23 activity.     

A molecular modeling based screening for potential inhibitors to alpha hemolysin from Staphylococcus aureus

Staphylococcus aureus, a Gram-positive bacterium is pathogenic in nature. It is known that secreted toxins remain active after antibiotic treatment. The alpha hemolysin or alpha toxin damages cell membrane and induces apoptosis and degradation of DNA. The titer of alphahemolysin increases and causes hemostasis disturbances, thrombocytopenia, and pulmonary lesions during staphylococcal infection. Therefore, it is of interest to inhibit alpha hemolysin using novel compounds. We used the structure of alpha hemolysin(PDB: 7AHL) to screen structures for 100,000 compounds from the ZINC database using molecular docking with AutoDock VINA. Nine (9) successive hits were then subjected for pharmacokinetic and toxicity properties by PROTOX (a webserver for the prediction of oral toxicities of small molecules) and FAFDrugs (a tool for prediction of ADME and Toxicity). This exercise further identified hit #1 ({[3a-(Dihydroxymethyl)-6-hydroxy-2,2-dimethyl-1,3,4-trioxatetrahydro-2H-pentalen-5- yl]methyl}amino(9H-fluoren-9-yl)acetate with binding affinity: -10.3 kcal/mol) and hit #2 (6-(Dihydroxymethyl)-2-{2-[3- (methylamino)propyl]-2-azatricyclo[9.4.0.03,8]pentadeca-1(11),3,5,7,12,14-hexaen-6-yloxy}tetrahydro-2H-pyran-3,4,5-triol with binding affinity: -9.6 kcal/mol) with acceptable toxicity and ADME properties for potential predicted hemolysin inhibition. These compounds should then be evaluated in vitro using inhibitory studies.