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Mahmoud M Habibullah,1,2 Syam Mohan,3,4 Nabeel Kashan Syed,5 Hafiz A Makeen,5 Qazi Mohammad Sajid Jamal,6 Hani Alothaid,7 Farkad Bantun,8 Alaa Alhazmi,1,2 Ali Hakamy,2,9 Yahia A Kaabi,1 Ghalia Samlan,10 Mohtashim Lohani,11 Neelaveni Thangavel,12 Mohamed Ahmed Al-Kasim5 1Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 2SMIRES for Consultation in Specialized Medical Laboratories, Jazan University, Jazan, Saudi Arabia; 3Substance Abuse and Toxicology Research Center, Jazan University, Jazan, Saudi Arabia; 4School of Health Science, University of Petroleum and Energy Studies, Dehradun, Uttarakhand, India; 5Pharmacy Practice Research Unit, Department of Clinical Pharmacy, Faculty of Pharmacy, Jazan University, Jazan, Saudi Arabia; 6Department of Health Informatics, College of Public Health and Health Informatics, Qassim University, Al Bukayriyah, Saudi Arabia; 7Department of Basic Sciences, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha, Saudi Arabia; 8Department of Microbiology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 9Respiratory Therapy Department, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 10Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia; 11Emergency Medical Services Department, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 12Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jazan University, Jazan, Saudi ArabiaCorrespondence: Mahmoud M Habibullah, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Al Maarefah Road, Jazan, Saudi Arabia, Tel +966 556644205, Email mhabibullah@jazanu.edu.saIntroduction: Numerous drugs with potent toxicity against cancer cells are available for treating malignancies, but therapeutic efficacies are limited due to their inefficient tumor targeting and deleterious effects on non-cancerous tissue. Therefore, two improvements are mandatory for improved chemotherapy 1) novel delivery techniques that can target cancer cells to deliver anticancer drugs and 2) methods to specifically enhance drug efficacy within tumors. The loading of inert drug carriers with anticancer agents and peptides which are able to bind (target) tumor-related proteins to enhance tumor drug accumulation and local cytotoxicity is a most promising approach.Objective: To evaluate the anticancer efficacy of Chitosan nanoparticles loaded with human growth hormone hGH fragment 176– 191 peptide plus the clinical chemotherapeutic doxorubicin in comparison with Chitosan loaded with doxorubicin alone.Methods: Two sets of in silico experiments were performed using molecular docking simulations to determine the influence of hGH fragment 176– 191 peptide on the anticancer efficacy of doxorubicin 1) the binding affinities of hGH fragment 176– 191 peptide to the breast cancer receptors, 2) the effects of hGH fragment 176– 191 peptide binding on doxorubicin binding to these same receptors. Further, the influence of hGH fragment 176– 191 peptide on the anticancer efficacy of doxorubicin was validated using viability assay in Human MCF-7 breast cancer cells.Results: In silico analysis suggested that addition of the hGH fragment to doxorubicin-loaded Chitosan nanoparticles can enhance doxorubicin binding to multiple breast cancer protein targets, while photon correlation spectroscopy revealed that the synthesized dual-loaded Chitosan nanoparticles possess clinically favorable particle size, polydispersity index, as well as zeta potential.Conclusion: These dual-loaded Chitosan nanoparticles demonstrated greater anti-proliferative activity against a breast cancer cell line (MCF-7) than doxorubicin-loaded Chitosan. This dual-loading strategy may enhance the anticancer potency of doxorubicin and reduce the clinical side effects associated with non-target tissue exposure.Keywords: anticancer potency, nanoparticles, cytotoxicity, docking analysis

Morganella morganii is a Gram-negative bacterial pathogen that causes bacteremia, urinary tract infections, intra-abdominal infections, chorioamnionitis, neonatal sepsis, and newborn meningitis. To control this bacterial pathogen a total of 3565 putative proteins targets in Morganella morganii were screened using comparative subtractive analysis of biochemical pathways annotated by the KEGG that did not share any similarities with human proteins. One of the targets, D-alanyl-D-alanine carboxypeptidase DacB [ Morganella ] was observed to be implicated in the majority of cell wall synthesis pathways, leading to its selection as a novel pharmacological target. The drug that interacted optimally with the identified target was observed to be Cefoperazone (DB01329) with the estimated free energy of binding -8.9 Kcal/mol. During molecular dynamics simulations; it was observed that DB01328-2exb and DB01329-2exb complexes showed similar values as the control FMX-2exb complex near 0.2 nm with better stability. Furthermore, MMPBSA total free energy calculation showed better binding energy than the control complex for DB01329-2exb interaction i.e. -31.50 (±0.93) kcal/mol. Our presented research suggested that D-alanyl-D-alanine carboxypeptidase DacB could be a therapeutic target and cefoperazone could be a promising ligand to inhibit the D-alanyl-D-alanine carboxypeptidase DacB protein of Morganella morganii . To identify prospective therapeutic and vaccine targets in Morganella morganii , this is the first computational and subtractive genomics investigation of various metabolic pathways exploring other therapeutic targets of Morganella morganii. In vitro/in vivo experimental validation of the identified target D-alanyl-D-alanine carboxypeptidase and the design of its inhibitors is suggested to figure out the best dose, the drug's effectiveness, and its toxicity.Communicated by Ramaswamy H. Sarma.

An imbalanced microbiome is linked to several diseases, such as cancer, inflammatory bowel disease, obesity, and even neurological disorders. Bacteria and their by-products are used for various industrial and clinical purposes. The metabolites under discussion were chosen based on their biological impacts on host and gut microbiota interactions as established by metabolome research. The separation of bacterial metabolites by using statistics and machine learning analysis creates new opportunities for applications of bacteria and their metabolites in the environmental and medical sciences. Thus, the metabolite production strategies, methodologies, and importance of bacterial metabolites for human well-being are discussed in this review.

Background: The hunt for naturally occurring antiviral compounds to combat viral infection was expedited when COVID-19 and Ebola spread rapidly. Phytochemicals from Nyctanthes arbor-tristis Linn were evaluated as significant inhibitors of these viruses. Methods: Computational tools and techniques were used to assess the binding pattern of phytochemicals from Nyctanthes arbor-tristis Linn to Ebola virus VP35, SARS-CoV-2 protease, Nipah virus glycoprotein, and chikungunya virus. Results: Virtual screening and AutoDock analysis revealed that arborside-C, beta amyrin, and beta-sitosterol exhibited a substantial binding affinity for specific viral targets. The arborside-C and beta-sitosterol molecules were shown to have binding energies of -8.65 and -9.11 kcal/mol, respectively, when interacting with the major protease. Simultaneously, the medication remdesivir exhibited a control value of -6.18 kcal/mol. The measured affinity of phytochemicals for the other investigated targets was -7.52 for beta-amyrin against Ebola and -6.33 kcal/mol for nicotiflorin against Nipah virus targets. Additional molecular dynamics simulation (MDS) conducted on the molecules with significant antiviral potential, specifically the beta-amyrin-VP35 complex showing a stable RMSD pattern, yielded encouraging outcomes. Conclusions: Arborside-C, beta-sitosterol, beta-amyrin, and nicotiflorin could be established as excellent natural antiviral compounds derived from Nyctanthes arbor-tristis Linn. The virus-suppressing phytochemicals in this plant make it a compelling target for both in vitro and in vivo research in the future.

The plant produced powerful secondary metabolites and showed strong antibacterial activities against food-spoiling bacterial pathogens. The present study aimed to evaluate antibacterial activities and to identify metabolites from the leaves and stems of Catharanthus roseus using NMR spectroscopy. The major metabolites likely to be observed in aqueous extraction were 2,3-butanediol, quinic acids, vindoline, chlorogenic acids, vindolinine, secologanin, and quercetin in the leaf and stem of the Catharanthus roseus . The aqueous extracts from the leaves and stems of this plant have been observed to be most effective against food spoilage bacterial strains, followed by methanol and hexane. However, leaf extract was observed to be most significant in terms of the content and potency of metabolites. The minimum inhibitory concentration (20 µg/mL) and bactericidal concentrations (35 g/mL) of leaf extract were observed to be significant as compared to the ampicillin. Molecular docking showed that chlorogenic acid and vindolinine strongly interacted with the bacterial penicillin-binding protein. The docking energies of chlorogenic acid and vindolinine also indicated that these could be used as food preservatives. Therefore, the observed metabolite could be utilized as a potent antibacterial compound for food preservation or to treat their illness, and further research is needed to perform.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are enzymes that break down and reduce the level of the neurotransmitter acetylcholine (ACh). This can cause a variety of cognitive and neurological problems, including Alzheimer's disease. Taxifolin is a natural phytochemical generally found in yew tree bark and has significant pharmacological properties, such as being anti-cancer, anti-inflammatory, and antioxidant. The binding affinity and inhibitory potency of taxifolin to these enzymes were evaluated through molecular docking and molecular dynamics simulations followed by the MMPBSA approach, and the results were significant. Taxifolin's affinity for binding to the AChE-taxifolin complex was -8.85 kcal/mol, with an inhibition constant of 326.70 nM. It was observed to interact through hydrogen bonds. In contrast, the BChE-taxifolin complex binding energy was observed to be -7.42 kcal/mol, and it was significantly nearly equal to the standard inhibitor donepezil. The molecular dynamics and simulation signified the observed interactions of taxifolin with the studied enzymes. The MMPBSA total free energy of binding for AChE-taxifolin was -24.34 kcal/mol, while BChE-taxifolin was -16.14 kcal/mol. The present research suggests that taxifolin has a strong ability to bind and inhibit AChE and BChE and could be used to manage neuron-associated problems; however, further research is required to explore taxifolin's neurological therapeutic potential using animal models of Alzheimer's disease.

The leaves, flowers, seeds, and bark of the Nyctanthes arbor-tristis Linn plant have been pharmacologically evaluated to signify the medicinal importance traditionally described for various ailments. We evaluated the anti-inflammatory potentials of 26 natural compounds using AutoDock 4.2 and Molecular Dynamics (MDS) performed with the GROMACS tool. SwissADME evaluated ADME (adsorption, distribution, metabolism, and excretion) parameters. Arb_E and Beta-sito, natural compounds of the plant, showed significant levels of binding affinity against COX-1, COX-2, PDE4, PDE7, IL-17A, IL-17D, TNF-α, IL-1β, prostaglandin E2, and prostaglandin F synthase. The control drug celecoxib exhibited a binding energy of -9.29 kcal/mol, and among the tested compounds, Arb_E was the most significant (docking energy: -10.26 kcal/mol). Beta_sito was also observed with high and considerable docking energy of -8.86 kcal/mol with the COX-2 receptor. COX-2 simulation in the presence of Arb_E and control drug celecoxib, RMSD ranged from 0.15 to 0.25 nm, showing stability until the end of the simulation. Also, MM-PBSA analysis showed that Arb_E bound to COX-2 exhibited the lowest binding energy of -277.602 kJ/mol. Arb_E and Beta_sito showed interesting ADME physico-chemical and drug-like characteristics with significant drug-like effects. Therefore, the studied natural compounds could be potential anti-inflammatory molecules and need further in vitro/in vivo experimentation to develop novel anti-inflammatory drugs.

Neurodegenerative disorders, such as Alzheimer's disease (AD), negatively affect the economic and psychological system. For AD, there is still a lack of disease-altering treatments and promising cures due to its complex pathophysiology. In this study, we computationally screened the natural database of fungal metabolites against three known therapeutic target proteins of AD. Initially, a pharmacophore-based, drug-likeness category was employed for screening, and it filtered the 14 ( A - N ) best hits out of 17,544 fungal metabolites. The 14 best hits were docked individually against GSK-3β, the NMDA receptor, and BACE-1 to investigate the potential of finding a multitarget inhibitor. We found that compounds B , F , and L were immuno-toxic, whereas E , H , I , and J had a higher LD 50 dose (5000 mg/kg). Among the examined metabolites, the Bisacremine-C (compound I ) was found to be the most active molecule against GSK-3β (ΔG: -8.7 ± 0.2 Kcal/mol, Ki: 2.4 × 10 6 M -1 ), NMDA (ΔG: -9.5 ± 0.1 Kcal/mol, Ki: 9.2 × 10 6 M -1 ), and BACE-1 (ΔG: -9.1 ± 0.2 Kcal/mol, Ki: 4.7 × 10 6 M -1 ). It showed a 25-fold higher affinity with GSK-3β, 6.3-fold higher affinity with NMDA, and 9.04-fold higher affinity with BACE-1 than their native ligands, respectively. Molecular dynamic simulation parameters, such as RMSD, RMSF, Rg, and SASA, all confirmed that the overall structures of the targeted enzymes did not change significantly after binding with Bisacremine-C, and the ligand remained inside the binding cavity in a stable conformation for most of the simulation time. The most significant hydrophobic contacts for the GSK-3β-Bisacremine-C complex are with ILE62, VAL70, ALA83, and LEU188, whereas GLN185 is significant for H-bonds. In terms of hydrophobic contacts, TYR184 and PHE246 are the most important, while SER180 is vital for H-bonds in NMDA-Bisacremine-C. THR232 is the most crucial for H-bonds in BACE-1-Bisacremine-C and ILE110-produced hydrophobic contacts. This study laid a foundation for further experimental validation and clinical trials regarding the biopotency of Bisacremine-C.

The complexity of Alzheimer's disease (AD) and several side effects of currently available medication inclined us to search for a novel natural cure by targeting multiple key regulatory proteins. We initially virtually screened the natural product-like compounds against GSK3β, NMDA receptor, and BACE-1 and thereafter validated the best hit through molecular dynamics simulation (MDS). The results demonstrated that out of 2029 compounds, only 51 compounds exhibited better binding interactions than native ligands, with all three protein targets (NMDA, GSK3β, and BACE) considered multitarget inhibitors. Among them, F1094-0201 is the most potent inhibitor against multiple targets with binding energy -11.7, -10.6, and -12 kcal/mol, respectively. ADME-T analysis results showed that F1094-0201 was found to be suitable for CNS drug-likeness in addition to their other drug-likeness properties. The MDS results of RMSD, RMSF, Rg, SASA, SSE and residue interactions indicated the formation of a strong and stable association in the complex of ligands (F1094-0201) and proteins. These findings confirm the F1094-0201's ability to remain inside target proteins' binding pockets while forming a stable complex of protein-ligand. The free energies (MM/GBSA) of BACE-F1094-0201, GSK3β-F1094-0201, and NMDA-F1094-0201 complex formation were -73.78 ± 4.31 kcal mol -1 , -72.77 ± 3.43 kcal mol -1 , and -52.51 ± 2.85 kcal mol -1 , respectively. Amongst the target proteins, F1094-0201 have a more stable association with BACE, followed by NMDA and GSK3β. These attributes of F1094-0201 indicate it as a possible option for the management of pathophysiological pathways associated with AD.

Alzheimer's disease (AD), the most common type of dementia in older people, causes neurological problems associated with memory and thinking. The key enzymes involved in Alzheimer's disease pathways are acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Because of this, there is a lot of interest in finding new AChE inhibitors. Among compounds that are not alkaloids, flavonoids have stood out as good candidates. The apple fruit, Malus domestica (Rosaceae), is second only to cranberries regarding total phenolic compound concentration. Computational tools and biological databases were used to investigate enzymes and natural compounds. Molecular docking techniques were used to analyze the interactions of natural compounds of the apple with enzymes involved in the central nervous system (CNS), acetylcholinesterase, and butyrylcholinesterase, followed by binding affinity calculations using the AutoDock tool. The molecular docking results revealed that CID: 107905 exhibited the best interactions with AChE, with a binding affinity of -12.2 kcal/mol, and CID: 163103561 showed the highest binding affinity with BuChE, i.e., -11.2 kcal/mol. Importantly, it was observed that amino acid residue Trp286 of AChE was involved in hydrogen bond formation, Van Der Walls interactions, and Pi-Sigma/Pi-Pi interactions in the studied complexes. Moreover, the results of the Molecular Dynamics Simulation (MDS) analysis indicated interaction stability. This study shows that CID: 12000657 could be used as an AChE inhibitor and CID: 135398658 as a BuChE inhibitor to treat Alzheimer's disease and other neurological disorders.

Indole-tethered chromene derivatives were synthesised in a one-pot multicomponent reaction using N -alkyl-1 H -indole-3-carbaldehydes, 5,5-dimethylcyclohexane-1,3-dione, and malononitrile, catalysed by DBU at 60-65 °C in a short reaction time. The benefits of the methodology include non-toxicity, an uncomplicated set-up procedure, a faster reaction time, and high yields. Moreover, the anticancer properties of the synthesised compounds were tested against selected cancer cell lines. The derivatives 4c and 4d displayed very good cytotoxic activity, with IC 50 values ranging from 7.9 to 9.1 µM. Molecular docking revealed the potent derivatives have good binding affinity towards tubulin protein, better than the control, and the molecular dynamic simulations further demonstrated the stability of ligand-receptor interactions. Moreover, the derivatives followed all the drug-likeness filters.

Microbes are ubiquitous in the biosphere, and their therapeutic and ecological potential is not much more explored and still needs to be explored more. The bacilli are a heterogeneous group of Gram-negative and Gram-positive bacteria. Lysinibacillus are dominantly found as motile, spore-forming, Gram-positive bacilli belonging to phylum Firmicutes and the family Bacillaceae . Lysinibacillus species initially came into light due to their insecticidal and larvicidal properties. Bacillus thuringiensis , a well-known insecticidal Lysinibacillus , can control many insect vectors, including a malarial vector and another, a Plasmodium vector that transmits infectious microbes in humans. Now its potential in the environment as a piece of green machinery for remediation of heavy metal is used. Moreover, some species of Lysinibacillus have antimicrobial potential due to the bacteriocin, peptide antibiotics, and other therapeutic molecules. Thus, this review will explore the biological disease control abilities, food preservative, therapeutic, plant growth-promoting, bioremediation, and entomopathogenic potentials of the genus Lysinibacillus .

We report microwave synthesis of seven unique pyrimidine anchored derivatives ( 1 - 7 ) incorporating multifunctional amino derivatives along with their in vitro anticancer activity and their activity against COVID-19 in silico. 1 - 7 were characterized by different analytical and spectroscopic techniques. Cytotoxic activity of 1 - 7 was tested against HCT116 and MCF7 cell lines, whereby 6 exhibited highest anticancer activity on HCT116 and MCF7 with EC 50 values of 89.24 ± 1.36 µM and 89.37 ± 1.17 µM, respectively. Molecular docking was performed for derivatives ( 1 - 7 ) on main protease for SARS-CoV-2 (PDB ID: 6LU7). Results revealed that most of the derivatives had superior or equivalent affinity for the 3CLpro, as determined by docking and binding energy scores. 6 topped the rest with highest binding energy score of -8.12 kcal/mol with inhibition constant reported as 1.11 µM. ADME, drug-likeness, and pharmacokinetics properties of 1 - 7 were tested using Swiss ADME tool. Toxicity analysis was done with pkCSM online server. All derivatives showed high GI absorption. Except 1 and 3 , all derivatives showed blood brain barrier permeability. Most derivatives showed negative logKp values suggesting derivatives are less skin permeable and bioavailability score of all derivatives was 0.55. The toxicity analysis demonstrated that all derivatives have no skin sensitization properties. 6 and 7 showed maximum tolerated dose (Human) values of -0.03 and -0.018, respectively and absence of AMES toxicity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Swansea University's United Kingdom (UK) Multiple Sclerosis (MS) Register is a platform that contains information on more than 17,600 people with MS living in the UK. The register has been in operation since 2011 and represents comprehensive information about people living with MS in the UK. It is considered the first register of its kind that can link information from patients to clinical data and has been established to answer different information needs about MS. Aim : To elucidate the trends in patterns of medicines currently used by people with MS in the UK MS register. Methods : This study follows an exploratory descriptive design using the UK MS register as data resource. A number of 4516 people completed the EQ-5D survey out of 8736 people who have given their consent to answer online questionnaires which represents around 52% of the register total population. Descriptive analysis and tests were performed with SPSS to address the research objectives. Results : There are several medicine names entered by people with MS in their profiles. These medicines are used either to manage MS symptoms or to treat its associated complications. Among the medicine types revealed in this study, disease modifying drugs (DMDs), muscle relaxants, and anticonvulsants are the medicine types mainly used by people with MS followed by antidepressant and antianxiety medicines. Conclusions : From the antidepressants used most widely, amitriptyline was chosen as a subject medicine for further investigation in the remaining studies of this research due to its high frequency use, the elevated depression rates discovered among people with MS who seek information on it online, and the high online content noted on websites about this medicine.

Several human diseases are caused by viruses, including cancer, Type I diabetes, Alzheimer's disease, and hepatocellular carcinoma. In the past, people have suffered greatly from viral diseases such as polio, mumps, measles, dengue fever, SARS, MERS, AIDS, chikungunya fever, encephalitis, and influenza. Recently, COVID-19 has become a pandemic in most parts of the world. Although vaccines are available to fight the infection, their safety and clinical trial data are still questionable. Social distancing, isolation, the use of sanitizer, and personal productive strategies have been implemented to prevent the spread of the virus. Moreover, the search for a potential therapeutic molecule is ongoing. Based on experiences with outbreaks of SARS and MERS, many research studies reveal the potential of medicinal herbs/plants or chemical compounds extracted from them to counteract the effects of these viral diseases. COVID-19's current status includes a decrease in infection rates as a result of large-scale vaccination program implementation by several countries. But it is still very close and needs to boost people's natural immunity in a cost-effective way through phytomedicines because many underdeveloped countries do not have their own vaccination facilities. In this article, phytomedicines as plant parts or plant-derived metabolites that can affect the entry of a virus or its infectiousness inside hosts are described. Finally, it is concluded that the therapeutic potential of medicinal plants must be analyzed and evaluated entirely in the control of COVID-19 in cases of uncontrollable SARS infection.

Anthraquinones (AQs) are present in foods, dietary supplements, pharmaceuticals, and traditional treatments and have a wide spectrum of pharmacological activities. In the search for anti-cancer drugs, AQ derivatives are an important class. In this study, anthraquinone aglycons chrysophanol (Chr), emodin (EM) and FDA-approved anticancer drug fluorouracil were analyzed by molecular docking studies against receptor molecules caspase-3, apoptosis regulator Bcl-2, TRAF2 and NCK-interacting protein kinase (TNIK) and cyclin-dependent protein kinase 2 (CDK2) as novel candidates for future anticancer therapeutic development. The ADMET SAR database was used to predict the toxicity profile and pharmacokinetics of the Chr and EM. Furthermore, in silico results were validated by the in vitro anticancer activity against HCT-116 and HeLa cell lines to determine the anticancer effect. According to the docking studies simulated by the docking program AutoDock Vina 4.0, Chr and EM had good binding energies against the target proteins. It has been observed that Chr and EM show stronger molecular interaction than that of the FDA-approved anticancer drug fluorouracil. In the in vitro results, Chr and EM demonstrated promising anticancer activity in HCT-116 and HeLa cells. These findings lay the groundwork for the potential use of Chr and EM in the treatment of human colorectal and cervical carcinomas.

Male infertility is a global public health concern. Teratozoospermia is a qualitative anomaly of spermatozoa morphology, contributing significantly to male infertility, whereas azoospermia is the complete absence of spermatozoa in the ejaculate. Thus, there is a serious need for unveiling the common origin and/or connection between both of these diseases, if any. This study aims to identify common potential biomarker genes of these two diseases via an in silico approach using a meta-analysis of microarray data. In this study, a differential expression analysis of genes was performed on four publicly available RNA microarray datasets, two each from teratozoospermia (GSE6872 and GSE6967) and azoospermia (GSE145467 and GSE25518). From the analysis, 118 DEGs were found to be common to teratozoospermia and azoospermia, and, interestingly, sperm autoantigenic protein 17 ( SPA17 ) was found to possess the highest fold change value among all the DEGs (9.471), while coiled-coil domain-containing 90B ( CCDC90B ) and coiled-coil domain-containing 91 ( CCDC91 ) genes were found to be common among three of analyses, i.e., Network Analyst, ExAtlas, and GEO2R. This observation indicates that SPA17, CCDC90B, and CCDC91 genes might have significant roles to play as potential biomarkers for teratozoospermia and azoospermia. Thus, our study opens a new window of research in this area and can provide an important theoretical basis for the diagnosis and treatment of both these diseases.

The free radicals produced by cigarette smoking are responsible for tissue damage, heart and lung diseases, and carcinogenesis. The effect of tobacco on the central nervous system (CNS) has received increased attention nowadays in research. Therefore, to explore the molecular interaction of cigarette smoke carcinogens (CSC) 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanol (NNAL), 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK), and N'-nitrosonornicotine (NNN) with well-known targets of CNS-related disorders, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) enzymes, a cascade of the computational study was conducted including molecular docking and molecular dynamics simulations (MDS). The investigated results of NNAL+AChE complex , NNK+AChE complex , and NNK+BuChE complex based on intermolecular energies (∆G) were found to -8.57 kcal/mol, -8.21 kcal/mol, and -8.08 kcal/mol, respectively. MDS deviation and fluctuation plots of the NNAL and NNK interaction with AChE and BuChE have shown significant results. Further, Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) results shown the best total binding energy ( Binding ∆G) -87.381 (+/-13.119) kJ/mol during NNK interaction with AChE. Our study suggests that CSC is well capable of altering the normal biomolecular mechanism of CNS; thus, obtained data could be useful to design extensive wet laboratory experimentation to know the effects of CSC on human CNS., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Protein tyrosine phosphatase-1B (PTP-1B) is a well-known therapeutic target for diabetes and obesity as it suppresses insulin and leptin signaling. PTP-1B deletion or pharmacological suppression boosted glucose homeostasis and insulin signaling without altering hepatic fat storage. Inhibitors of PTP-1B may be useful in the treatment of type 2 diabetes, and shikonin, a naturally occurring naphthoquinone dye pigment, is reported to inhibit PTP-1B and possess antidiabetic properties. Since the cell contains a large number of phosphatases, PTP-1B inhibitors must be effective and selective. To explore more about the mechanism underlying the inhibitor's efficacy and selectivity, we investigated its top four pharmacophores and used site-directed mutagenesis to insert amino acid mutations into PTP-1B as an extension of our previous study where we identified 4 pharmacophores of shikonin. The study aimed to examine the site-directed mutations like R24Y, S215E, and S216C influence the binding of shikonin pharmacophores, which act as selective inhibitors of PTP-1B. To achieve this purpose, docking and molecular dynamics simulations of wild-type (WT) and mutant PTP-1B with antidiabetic compounds were undertaken. The simulation results revealed that site-directed mutations can change the hydrogen bond and hydrophobic interactions between shikonin pharmacophores and many residues in PTP-1B's active site, influencing the drug's binding affinity. These findings could aid researchers in better understanding PTP-1B inhibitors' selective binding mechanism and pave the path for the creation of effective PTP-1B inhibitors.

Natural resources, particularly plants and microbes, are an excellent source of bioactive molecules. Bromelain, a complex enzyme mixture found in pineapples, has numerous pharmacological applications. In a search for therapeutic molecules, we conducted an in silico study on natural phyto-constituent bromelain, targeting pathogenic bacteria and viral proteases. Docking studies revealed that bromelain strongly bound to food-borne bacterial pathogens and SARS-CoV-2 virus targets, with a high binding energy of -9.37 kcal/mol. The binding interaction was mediated by the involvement of hydrogen bonds, and some hydrophobic interactions stabilized the complex and molecular dynamics. Simulation studies also indicated the stable binding between bromelain and SARS-CoV-2 protease as well as with bacterial targets which are essential for DNA and protein synthesis and are required to maintain the integrity of membranous proteins. From this in silico study, it is also concluded that bromelain could be an effective molecule to control foodborne pathogen toxicity and COVID-19. So, eating pineapple during an infection could help to interfere with the pathogen attaching and help prevent the virus from getting into the host cell. Further, research on the bromelain molecule could be helpful for the management of COVID-19 disease as well as other bacterial-mediated diseases. Thus, the antibacterial and anti-SARS-CoV-2 virus inhibitory potentials of bromelain could be helpful in the management of viral infections and subsequent bacterial infections in COVID-19 patients.

The COVID-19 era has prompted several researchers to search for a linkage between COVID-19 and its associated neurological manifestation. Toll-like receptor 4 (TLR-4) acts as one such connecting link. spike protein of SARS-CoV-2 can bind either to ACE-2 receptors or to TLR-4 receptors, leading to aggregation of α-synuclein and neurodegeneration via the activation of various cascades in neurons. Recently, dithymoquinone has been reported as a potent multi-targeting candidate against SARS-CoV-2. Thus, in the present study, dithymoquinone and its six analogues were explored to target 3CL pro (main protease of SARS-CoV-2), TLR4 and PREP (Prolyl Oligopeptidases) by using the molecular docking and dynamics approach. Dithymoquinone (DTQ) analogues were designed in order to investigate the effect of different chemical groups on its bioactivity. It is noteworthy to mention that attention was given to the feasibility of synthesizing these analogues by a simple photo-dimerisation reaction. The DTQ analogue containing the 4-fluoroaniline moiety [Compound ( 4 )] was selected for further analysis by molecular dynamics after screening via docking-interaction analyses. A YASARA structure tool built on the AMBER14 force field was used to analyze the 100 ns trajectory by taking 400 snapshots after every 250 ps. Moreover, RMSD, RoG, potential energy plots were successfully obtained for each interaction. Molecular docking results indicated strong interaction of compound ( 4 ) with 3CL pro , TLR4 and PREP with a binding energy of -8.5 kcal/mol, -10.8 kcal/mol and -9.5 kcal/mol, respectively, which is better than other DTQ-analogues and control compounds. In addition, compound ( 4 ) did not violate Lipinski's rule and showed no toxicity. Moreover, molecular dynamic analyses revealed that the complex of compound ( 4 ) with target proteins was stable during the 100 ns trajectory. Overall, the results predicted that compound ( 4 ) could be developed into a potent anti-COVID agent with the ability to mitigate neurological manifestations associated with COVID-19.

The association of COVID-19 with neurological complications is a well-known fact, and researchers are endeavoring to investigate the mechanistic perspectives behind it. SARS-CoV-2 can bind to Toll-like receptor 4 (TLR-4) that would eventually lead to α-synuclein aggregation in neurons and stimulation of neurodegeneration pathways. Olive leaves have been reported as a promising phytotherapy or co-therapy against COVID-19, and oleuropein is one of the major active components of olive leaves. In the current study, oleuropein was investigated against SARS-CoV-2 target (main protease 3CL pro ), TLR-4 and Prolyl Oligopeptidases (POP), to explore oleuropein potency against the neurological complications associated with COVID-19. Docking experiments, docking validation, interaction analysis, and molecular dynamic simulation analysis were performed to provide insight into the binding pattern of oleuropein with the three target proteins. Interaction analysis revealed strong bonding between oleuropein and the active site amino acid residues of the target proteins. Results were further compared with positive control lopinavir (3CL pro ), resatorvid (TLR-4), and berberine (POP). Moreover, molecular dynamic simulation was performed using YASARA structure tool, and AMBER14 force field was applied to examine an 100 ns trajectory run. For each target protein-oleuropein complex, RMSD, RoG, and total potential energy were estimated, and 400 snapshots were obtained after each 250 ps. Docking analyses showed binding energy as -7.8, -8.3, and -8.5 kcal/mol for oleuropein-3CL pro , oleuropein-TLR4, and oleuropein-POP interactions, respectively. Importantly, target protein-oleuropein complexes were stable during the 100 ns simulation run. However, an experimental in vitro study of the binding of oleuropein to the purified targets would be necessary to confirm the present study outcomes.

Diabetes is a complicated multifactorial disorder in which the patient generally observes polyphagia, polydipsia, and polyuria due to uncontrolled growth in blood sugar levels. For its management, the pharmaceutical industry is working day and night to find a better drug with no or least toxicity. That's why nowadays a more focused branch is to use herbal phytoconstituents for its prevention. Shikonin is a naphthoquinone natural dye that is isolated from the plants of the Boraginaceae family and has proven its role as an anti-cancer, anti-inflammatory, and anti-gonadotrophic agent. In our previous study, we have published its anti-diabetic action by inhibiting the enzyme protein tyrosine phosphatase 1B. In this study, we were more focused on finding out the role of Shikonin and its pharmacophores by inhibiting the action of aldose reductase (AR) enzyme. The study was conducted using pharmacophore modeling, molecular docking, and molecular dynamics simulation studies. The absorption, distribution, metabolism, excretion (ADME), and toxicity profile were also evaluated in this study. Along with all the computational biology parameters we also focused on the in vitro activity and kinetic study of inhibitory activity of Shikonin against aldose reductase., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Gastric cancer is the fifth most frequent cancer and the third major cause of mortality worldwide. Helicobacter pylori , a bacterial infection linked with GC, injects the cytotoxin-associated antigen A (CagA; an oncoprotein) into host cells. When the phosphorylated CagA protein enters the cell, it attaches to other cellular components, interfering with normal cellular signaling pathways. CagA plays an important role in the progression of GC by interacting with phosphatidylserine of the host cell membrane. Therefore, disrupting the CagA-phosphatidylserine connection using small molecules appears to be a promising therapeutic approach. In this report, we screened the natural compounds from ZINC database against the CagA protein using the bioinformatics tools. Hits were initially chosen based on their physicochemical, absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics, as well as other drug-like characteristics. To locate safe and effective hits, the PAINS filter, binding affinities estimation, and interaction analysis were used. Three compounds with high binding affinity and specificity for the CagA binding pocket were discovered. The final hits, ZINC153731, ZINC69482055, and ZINC164387, were found to bind strongly with CagA protein, with binding energies of -11.53, -10.67, and -9.21 kcal/mol, respectively, which were higher than that of the control compound (-7.25 kcal/mol). Further, based on binding affinity and interaction pattern, two leads (ZINC153731, ZINC69482055) were chosen for molecular dynamics (MD) simulation analysis. MD results showed that they displayed stability in their vicinity at 100 ns. This study suggested that these compounds could be used as possible inhibitors of CagA protein in the fight against GC. However, additional benchwork tests are required to validate them as CagA protein inhibitors.

An efficient atom-economical synthetic protocol to access new imidazole-based N -phenylbenzamide derivatives is described. A one-pot three-component reaction was utilized to provide a series of N-phenylbenzamide derivatives in a short reaction time (2-4 h) with an 80-85% yield. The cytotoxic evaluation revealed that derivatives 4e and 4f exhibited good activity, with IC 50 values between 7.5 and 11.1 μM against the tested cancer cell lines. Computational studies revealed interesting insights: the docking of the active derivatives (4e and 4f) showed a higher affinity toward the target receptor protein than the control. Molecular dynamic simulations revealed that the active derivatives form stable complexes with the ABL1 kinase protein. Moreover, the ADME and drug-likeness of the derivatives reinforced the potential of the derivatives to be taken up for further development as anticancer agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with one of the authors ZM., (Copyright © 2022 Malik, Alsantali, Jamal, Seddigi, Morad, Alsharif, Hussein, Jassas, Al-Rooqi, Abduljaleel, Babalgith, Altass, Moussa and Ahmed.)

Background: In late 2019, a highly infectious and pathogenic coronavirus was recognized as Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2), which causes acute respiratory disease, threatening human health and public safety. A total of 448,327,303 documented cases and 6,028,576 deaths have been reported as of March 8th 2022. The COVID-19 vaccines currently undergoing clinical trials or already in use should provide at least some protection against SARS-CoV-2; however, the emergence of new variations as a result of mutations may lessen the effectiveness of the currently available vaccines. Since the efficacy of available drugs and vaccines against COVID-19 is notably lower, there is an urgent need to develop a potential drug to treat this deadly disease. The SARS-CoV-2 spike (SCoV-SG) is the foremost drug target among coronaviruses., Objective: The major objectives of the current study are to conduct a molecular docking study investigation of TAT-peptide 47-57 (GRKKRRQRRRP)-conjugated remodified therapeutics such as ritonavir (RTV), lopinavir (LPV), favipiravir (FPV), remdesivir (RMV), hydroxychloroquine (HCQ), molnupiravir (MNV) and nirmatrelvir (NMV) with (SCoV-SG) structure., Methods: Molecular docking analysis was performed to study the interaction of repurposed drugs and drugs conjugated with the TAT-peptide with target SARS-CoV-2 spike glycoprotein (PDB ID: 6VYB) using Auto- Dock. Further docking investigation was completed with PatchDock and was visualized by the discovery of the studio visualizer 2020., Results: TAT-peptides are well-characterized immune enhancers that are used in intracellular drug delivery. The results of molecular docking analysis showed higher efficiency and significantly enhanced and improved interactions between TP-conjugated repurposed drugs and the target sites of the SCoV-SG structure., Conclusion: The study concluded that TP-conjugated repurposed drugs may be effective in preventing COVID- 19, and therefore, in vitro, in vivo, and clinical trial studies are required in detail., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Vibrio cholerae causes the diarrheal disease cholera which affects millions of people globally. The outer membrane protein U (OmpU) is the outer membrane protein that is most prevalent in V. cholerae and has already been recognized as a critical component of pathogenicity involved in host cell contact and as being necessary for the survival of pathogenic V. cholerae in the host body. Computational approaches were used in this study to screen a total of 37,709 natural compounds from the traditional Chinese medicine (TCM) database against the active site of OmpU. Following a sequential screening of the TCM database, we report three lead compounds-ZINC06494587, ZINC85510056, and ZINC95910434-that bind strongly to OmpU, with binding affinity values of -8.92, -8.12, and -8.78 kcal/mol, which were higher than the control ligand (-7.0 kcal/mol). To optimize the interaction, several 100 ns molecular dynamics simulations were performed, and the resulting complexes were shown to be stable in their vicinity. Additionally, these compounds were predicted to have good drug-like properties based on physicochemical properties and ADMET assessments. This study suggests that further research be conducted on these compounds to determine their potential use as cholera disease treatment.

The human-to-human transmitted respiratory illness in COVID-19 affected by the pathogenic Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), which appeared in the last of December 2019 in Wuhan, China, and rapidly spread in many countries. Thereon, based on the urgent need for therapeutic molecules, we conducted in silico based docking and simulation molecular interaction studies on repurposing drugs, targeting SARS-CoV-2 spike protein. Further, the best binding energy of doxorubicin interacting with virus spike protein (PDB: 6VYB) was observed to be -6.38  kcal/mol and it was followed by exemestane and gatifloxacin. The molecular simulation dynamics analysis of doxorubicin, Reference Mean Square Deviation (RMSD), Root Mean Square fluctuation (RMSF), Radius of Gyration (Rg), and formation of hydrogen bonds plot interpretation suggested, a significant deviation and fluctuation of Doxorubicin-Spike RBD complex during the whole simulation period. The Rg analysis has stated that the Doxorubicin-Spike RBD complex was stable during 15,000-35,000 ps MDS. The results have suggested that doxorubicin could inhibit the virus spike protein and prevent the access of the SARS-CoV-2 to the host cell. Thus, in-vitro/in-vivo research on these drugs could be advantageous to evaluate significant molecules that control the COVID-19 disease., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier B.V. on behalf of King Saud University.)

Diabetes mellitus is a multifactorial disease that affects both developing and developed countries and is a major public health concern. Many synthetic drugs are available in the market, which counteracts the associated pathologies. However, due to the propensity of side effects, there is an unmet need for the investigation of safe and effective drugs. This research aims to find a novel phytoconstituent having diminished action on blood glucose levels with the least side effects. Shikonin is a naturally occurring naphthoquinone dying pigment obtained by the roots of the Boraginaceae family. Besides its use as pigments, it can be used as an antimicrobial, anti-inflammatory, and anti-tumor agent. This research aimed to hypothesize the physicochemical and phytochemical properties of Shikonin's in silico interaction with protein tyrosine phosphate 1B, as well as it's in vitro studies, in order to determine its potential anti-diabetic impact. To do so, molecular docking experiments with target proteins were conducted to assess their anti-diabetic ability. Analyzing associations with corresponding amino acids revealed the significant molecular interactions between Shikonin and diabetes-related target proteins. In silico pharmacokinetics and toxicity profile of Shikonin using ADMET Descriptor, Toxicity Prediction, and Calculate Molecular Properties tools from Biovia Discovery Studio v4.5. Filter by Lipinski and Veber Rule's module from Biovia Discovery Studio v4.5 was applied to assess the drug-likeness of Shikonin. The in vitro studies exposed that Shikonin shows an inhibitory potential against the PTP1B with an IC50 value of 15.51 µM. The kinetics studies revealed that it has a competitive inhibitory effect (Ki = 7.5 M) on the enzyme system, which could be useful in the production of preventive and therapeutic agents. The findings of this research suggested that the Shikonin could be used as an anti-diabetic agent and can be used as a novel source for drug delivery.

Background: Human health issues caused by Cigarette Smoke Carcinogens (CSC) are increasing rapidly every day and challenging the scientific community to provide a better understanding in order to avoid its impact on communities. Cigarette smoke also contains tobacco-based chemical compounds harmful to human beings, either smokers or non-smokers., Objective: We have tested 7H-Dibenzo[c,g]carbazole (7H-DBC) and Dibenz[a,h]acridine (DBAD) derivatives of Asz-arenes along with N'-Nitrosoanabasine (NAB) and N-Nitrosoanatabine (NAT) derivatives of N-Nitrosamines molecular interaction with CNS biomolecules., Methods: Computational synergistic approaches like system biology and molecular interaction techniques were implemented to conduct the analysis., Results: CSC efficiently interacted with NRAS, KRAS, CDH1, and RAC1 molecular targets in CNS. We have also performed the interactome analysis followed by system biology approaches and found that HSPA8 is the most important hub protein for the network generated for CSC-hampered genes of CNS. We have also identified 6 connector proteins, namely TP53, HSP90AA1, PPP2CA, CDH1, CTNNB1, and ARRB1. Further analysis revealed that NRAS and CDH1 have maximum interactions with all the selected CSC., Conclusion: The obtained structural analysis data could be utilized to assess the carcinogenic effect of CSC and could be useful in the treatment of CNS diseases and disorders induced, especially by tobacco-specific carcinogens, or it could also be used in vivo/ in vitro experimentation model designing., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that originated in Chinese city of Wuhan has caused around 906,092 deaths and 28,040,853 confirmed cases worldwide (https://covid19.who.int/, 11 September 2020). In a life-threatening situation, where there is no specific and licensed anti-COVID-19 vaccine or medicine available; the repurposed drug might act as a silver bullet. Currently, more than 211 vaccines, 80 antibodies, 31 antiviral drugs, 35 cell-based, 6 RNA-based and 131 other drugs are in clinical trials. It is therefore utter need of the hour to develop an effective drug that can be used for the treatment of COVID-19 before a vaccine can be developed. One of the best-characterized and attractive drug targets among coronaviruses is the main protease (3CL pro ). Therefore, the current study focuses on the molecular docking analysis of TAT-peptide 47-57 (GRKKRRQRRRP)-conjugated repurposed drugs (i.e., lopinavir, ritonavir, favipiravir, and hydroxychloroquine) with SARS-CoV-2 main protease (3CL pro ) to discover potential efficacy of TAT-peptide (TP) - conjugated repurposing drugs against SARS-CoV-2. The molecular docking results validated that TP-conjugated ritonavir, lopinavir, favipiravir, and hydroxychloroquine have superior and significantly enhanced interactions with the target SARS-CoV-2 main protease. In-silico approach employed in this study suggests that the combination of the drug with TP is an excelling alternative to develop a novel drug for the treatment of SARS-CoV-2 infected patients. The development of TP based delivery of repurposing drugs might be an excellent approach to enhance the efficacy of the existing drugs for the treatment of COVID-19. The predictions from the results obtained provide invaluable information that can be utilized for the choice of candidate drugs for in vitro, in vivo and clinical trials. The outcome from this work prove crucial for exploring and developing novel cost-effective and biocompatible TP conjugated anti-SARS-CoV-2 therapeutic agents in immediate future., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Published by Elsevier B.V. on behalf of King Saud University.)

Background and Objective: Topoisomerase TOP-IIA (TTOP-IIA) is widely used as a significant target for cancer therapeutics because of its involvement in cell proliferation. Steroidal drugs have been suggested for breast cancer treatment as aromatase enzymes inhibitors . TTOP-IIA inhibitors can be used as a target for the development of new cancer therapeutics., Materials and Methods: In this study, we conducted a docking study on steroidal drugs Anastrozole (ANA), Letrozole (LET), and exemestane (EXE) with TTOP-IIA  to explore the therapeutic area of these drugs., Results: The binding interaction of EXE drug had significant docking interaction which is followed by ANA and LET. Thus, all these drugs could be used to inhibit the TTOP-IIA mediated cell proliferation and could be a hope to treat the other types of cancers. Among all three tested steroidal drugs, EXE showed binding energy -7.05 kcal/mol, hydrogen bond length1.78289 Å and amino acid involved in an interaction was A: LYS723:HZ3 -: UNK1:O6., Conclusion: The obtained data showed the most significant binding interaction analyzed with the tested enzyme. Thus, in vitro laboratory experimentation and in vivo research are necessary to put forward therapeutic repositioning of these drugs to establish them as a broad spectrum potential anticancer drugs., .

Keeping in view the public health-related issues of Alzheimer's disease (AD), its unpredictable occurrence and progression indicate the needs for best treatment options. The present bioinformatics study explores the binding pattern and molecular interactions between human acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes with natural compounds from Bacopa monnieri. The docking analysis between natural compounds as a ligand and AChE, BuChE as a receptor was completed using MGL tools Autodock 4.2 module. The analysis of the hydrophobic interactions, inhibition constants, and hydrogen bonds may indicates that they play a significant role in finding out the interacting position at the active site. However, after analyzing the binding energy (ΔG), the documented data shows that bacoside X, bacoside A, 3-beta-D-glucosylstigmasterol and daucosterol could be good inhibitors in the inhibition of AChE and BuChE activities. Therefore, our study indicates that the inhibition constants of the aforesaid natural compounds of Bacopa can be utilized for the development of inhibitors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Malignant tumors are the leading cause of death in humans. Due to the tedious efforts and investigations made in the field of marine drug discovery, there is now a scientific bridge between marine and pharmaceutical sciences. However, currently only few marine drugs have been lined towards anticancer direction yet many more to are be established in future as well., Method: This review gives an overview of present status of marine natural products MNPs both at the level of research and clinical stages. The authors haved summarized the detail information of diverse marine organisms that were reportedto be active or potentially active in cancer treatment in the last two decades. Interstingly, marine organisms are abundant producer of plenty of structurally incomparable bioactive metabolites that have unusual mode of actions and diverse biosynthetic pathways., Results: This review summarizes the associated anticancer properties of different classes of marine natural compounds based on their structural diversity, biological activity, and the molecular mechanisms of action. Emphasis has also be given to recent advances in clinical development of marine agents used in clinical trials., Conclusions: The present review is summarising the various sources of marine chemicals and their exploration of anticancerous potential. There is justified hope for the discovery and development of new anticancer agents from the marine environment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Designing a novel antagonist against VEGFR-2 is being applied currently to inhibit cancer growth and metastasis. Because of the unexpected side effects incurred by the contemporary anticancer medications, the focus has been laid towards identifying natural compounds that might carry the potential to inhibit tumor progression. VEGR-2 remains an important target for anticancer drug development as it is the master regulator of vascular growth., Objective: The study focuses on virtual screening of compounds from plants of Asteraceae family that bears antiangiogenic potential and thus, inhibiting VEGFR-2 using a computational approach., Materials and Methods: Structures of phytochemicals were prepared using ChemDraw Ultra 10 software and converted into its 3D PDB structure and minimized using Discovery Studio client 2.5. The target protein, VEGFR-2 was retrieved from RCSB PDB. Lipinski's rule and ADMET toxicity profiling were carried out on the phytochemicals of the Asteraceae family and the filtered compounds were further promoted for molecular docking and MD simulation analysis. The study extends towards the SOM analysis of Pinocembrin to predict the possible toxic and non-toxic in vivo metabolites via in silico tools (Xenosite Web and PASS online server)., Results: The docking results revealed promising inhibitory potential of Pinocembrin against VEGFR-2 with binding energy of -8.50 kcal/mole as compared to its known inhibitors Sorafenib and YLT192 having binding energy of -6.49 kcal/mole and -8.02 kcal/mol respectively. Further, molecular dynamics (MD) simulations for 10ns were conducted for optimization, flexibility prediction, and determination of folded VEGFR-2 stability. The Hsp90-Pinocembrin complex was found to be quite stable with RMSD value of 0.2nm. Pinocembrin was found to be metabolically stable undergoing phase I metabolism with non-toxic metabolites compared to the standard drug Sorafenib and YLT192., Conclusion: Obtained results propose Pinocembrin as a multi-targeted novel lead compound that bears outstanding antiangiogenic potential against VEGFR-2., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Bacteriocin have been tested as safe and effective alternative molecules over the currently used chemotherapeutic agents. Thus, being an important clinical significance, its screening and recovery methods along with its application are poorly described. Therefore, their screening, purification strategies and utilities must me extended. Thus, in this review, we, summarize potential application, various screening and purification methods used for recovery of bacteriocins., Methods: To complete this review, many reviews and previously published reports were studied. We, concentrated on review question and exclusion and inclusion criteria. The quality of content was evaluated by the quality the quality contents evaluation method. The standard method is used to describe the useful contents of available resources and appraised., Results: One hundred twenty research and review reports were used to complete this report. Sixty reports were used to make a collective information on screening and production of Bacteriocin Eighty two papers were used to explore the antimicrobial, therapeutic, diagnostic etc potentialities of bacteriocin in diverse field. The summarize form of data also presented in the form of tables and figures. This review describes the various methods and parameters that must be considered during the screening and purification methods. Moreover, the useful information is collected in regard represent it therapeutic potentialities in various fields for the welfare of human being., Conclusions: The conclusion of this review presented the significance of a fundamental framework for planning to understanding the basic requirement needed for fast, cost effective screening and purification of bacteriocins. The summered area of their utilities also helpful to extend the research field of bacteriocin. Thus, this report would be useful not only to scale up the screening and production strategies faster at economical rate, but also provides a platform to extend the research field of bacteriocin in many ways., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Due to the appearance of antibiotic resistance and the toxicity associated with currently used antibiotics, peptide antibiotics are the need of the hour. Thus, demand for new antimicrobial agents has brought great interest in new technologies to enhance safety. One such antimicrobial molecule is bacteriocin, synthesised by various micro-organisms. Bacteriocins are widely used in agriculture, veterinary medicine as a therapeutic, and as a food preservative agent to control various infectious and food-borne pathogens. In this review, we highlight the potential therapeutic and food preservative applications of bacteriocin., (Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Background: Lung cancer is one of the most fatal chronic diseases in the field of respiratory medicine. The purpose of this paper is to address the side effects of conventional treatment strategies and to report the findings of till date drug nanocarriers researches performed for lung cancer therapy. This review also highlights the outstanding results of several researches employing pulmonary delivery system of nano-based drug formulations suitable for lung cancer., Objective: Summarizing the advances made in the field of nanotechnology-based lung cancer management., Methods: We systematically searched for research literature using a well-framed review question and presented data in the tabular forms for readers' convenience., Results: Sixty-four papers were included in the review, the majority of which represent latest researches in the field of nanoparticle-based drug delivery for lung cancer therapy. Conventional treatment strategies for lung cancer lack specificity and are limited by undesirable toxicities in normal cells, as well as a high rate of recurrence. Intervention of nanotechnology has revolutionized the therapy of lung cancer upto a great extent by overcoming the current constraints in conventional therapies. Pulmonary delivery of nano-based drug formulations has resulted in potentially more effective and advanced lung cancer therapy., Conclusion: Several nanoscale drug delivery systems for lung cancer treatment are at present in clinical trials and some of them already exist in commercially available forms in the marketplace. However, although nanoscale drug carriers for lung cancer treatment have demonstrated stupendous therapeutic potential at both preclinical and clinical trials, but there are still many limitations to be solved., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Angiogenesis involves the process of sprouting of microvessels from preexisting microvasculature and is held responsible for the growth, malignancy and metastasis of cancer. Heat shock protein Hsp90 has been proven responsible for indirectly inducing multiple pathways leading to angiogenesis and metastasis in cancer. Recent researches shift towards proposing novel phytochemicals as possible antiangiogenic agents., Objective: The study aims towards Virtual screening of compounds from Cucurbitaceae family and their Druglikeliness and PreADMET filtering in search of potent lead as Vitexin, targeting Hsp90 and hence restraining angiogenesis., Materials and Methods: Structures of phytochemicals from Cucurbitaceae family were retrieved from PubChem database and were converted into suitable 3-D structures. The target protein, Hsp90 was retrieved from RCSB Protein Data Bank. Phytochemicals of Cucurbitaceae family were filtered through enumerated Lipinski's rule of five and ADMET toxicity profiling and the filtered compounds were further taken forward for molecular docking analysis and interaction studies using AutoDock Tools 4.0., Results: The docking results revealed Vitexin, a prominent glycosylated natural flavonoid, showing promising inhibitory potential against Hsp90 with binding energy of -8.80 kcal/mole and Ki 353.24 nM as compared to its known inhibitor Ganetespib having binding energy of -7.33 kcal/mole and Ki 4260 nM. Vitexin also exhibits better drug having properties with satisfactory ADMET profiling in relation to Ganetespib., Conclusion: The result proposes Vitexin to hold prominent antiangiogenic potential surpassing different in silico parameters and thus expected to be a multi-targeted novel antiangiogenic lead., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Brain, the centre of the nervous system and an integral part the body, is protected by two anatomical and physiological barriers- Blood-Brain Barrier (BBB) and Blood-Cerebrospinal Fluid Barrier (BCSFB). Blood-Brain Barrier is a very complex and highly organized multicellular structure that shields the brain from harmful substances and invading organisms from the bloodstream and thus offering protection against various brain diseases and injuries. However, it also impede the effective delivery of drug to the brain, thus, preventing treatment of numerous neurological disorders. Even though various traditional approaches such as Intra-Cerebro-Ventricular (ICV) injection, use of implants, disruption of BBB and use of prodrugs have achieved some success in overcoming these barriers, researchers are continuously working for promising alternatives for improved brain drug delivery. Recent breakthroughs in the field of nanotechnology provide an appropriate solution to problems associated with these delivery approaches and thus can be effectively used to treat a wide variety of brain diseases. Thus, nanotechnology promises to bring a great future to the individuals with various brain disorders. This review provides a brief overview of various brain drug delivery approaches along with limitations. In addition, the significance of nanoparticles as drug carrier systems for effective brain specific drug delivery has been highlighted. To show the complexity of the problems to be overcome for improved brain drug delivery, a concise intercellular classification of the BBB along with general transport routes across it is also included., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)