Mutational analysis of consanguineous families and their targeted therapy against dwarfism.

Dwarfism is a medical term used to describe individuals with a height-vertex measurement that falls below two standard deviations (-2SD) or the third percentile for their gender and age. Normal development of growth is a complicated dynamic procedure that depends upon the coordination of different aspects involving diet, genetics, and biological aspects like hormones in equilibrium. Any severe or acute pathologic procedure may disturb the individual's normal rate of growth. In this research, we examined four (A-D) Pakistani consanguineous families that exhibited syndromic dwarfism, which was inherited in an autosomal recessive pattern. The genomic DNA of each family member was extracted by using phenol-chloroform and Kit methods. Whole Exome Sequencing (WES) of affected family members (IV-11, III-5, IV-4 and III-13) from each group was performed at the Department of Medical Genetics, University of Antwerp, Belgium. After filtering the exome data, the mutations in PPM1F, FGFR3, ERCC2, and PCNT genes were determined by Sanger sequencing of each gene by using specific primers. Afterward, FGFR3 was found to be a suitable drug target among all the mutations to treat achondroplasia also known as disproportionate dwarfism. BioSolveIT softwares were used to discover the lead active inhibitory molecule against FGFR3. This research will not only provide short knowledge to the concerned pediatricians, researchers, and family physicians for the preliminary assessment and management of the disorder but also provide a lead inhibitor for the treatment of disproportionate dwarfism.Communicated by Ramaswamy H. Sarma.

Isolation, Identification, and Antibacterial Properties of Prodigiosin, a Bioactive Product Produced by a New Serratia marcescens JSSCPM1 Strain: Exploring the Biosynthetic Gene Clusters of Serratia Species for Biological Applications.

Prodigiosin pigment has high medicinal value, so exploring this compound is a top priority. This report presents a prodigiosin bioactive compound isolated from Serratia marcescens JSSCPM1, a new strain. The purification process of this compound involves the application of different chromatographic methods, including UV-visible spectroscopy, high-performance liquid chromatography (HPLC), and liquid chromatography-mass spectrometry (LC/MS). Subsequent analysis was performed using nuclear magnetic resonance (NMR) to achieve a deeper understanding of the compound's structure. Finally, through a comprehensive review of the existing literature, the structural composition of the isolated bioactive compound was found to correspond to that of the well-known compound prodigiosin. The isolated prodigiosin compound was screened for antibacterial activity against both Gram-positive and Gram-negative bacteria. The compound inhibited the growth of Gram-negative bacterial strains compared with Gram-positive bacterial strains. It showed a maximum minimum inhibitory concentration against Escherichia coli NCIM 2065 at a 15.9 ± 0.31 µg/mL concentration. The potential binding capabilities between prodigiosin and the OmpF porin proteins (4GCS, 4GCP, and 4GCQ) were determined using in silico studies, which are generally the primary targets of different antibiotics. Comparative molecular docking analysis indicated that prodigiosin exhibits a good binding affinity toward these selected drug targets.

Recent developments in natural biopolymer based drug delivery systems.

Targeted delivery of drug molecules to diseased sites is a great challenge in pharmaceutical and biomedical sciences. Fabrication of drug delivery systems (DDS) to target and/or diagnose sick cells is an effective means to achieve good therapeutic results along with a minimal toxicological impact on healthy cells. Biopolymers are becoming an important class of materials owing to their biodegradability, good compatibility, non-toxicity, non-immunogenicity, and long blood circulation time and high drug loading ratio for both macros as well as micro-sized drug molecules. This review summarizes the recent trends in biopolymer-based DDS, forecasting their broad future clinical applications. Cellulose chitosan, starch, silk fibroins, collagen, albumin, gelatin, alginate, agar, proteins and peptides have shown potential applications in DDS. A range of synthetic techniques have been reported to design the DDS and are discussed in the current study which is being successfully employed in ocular, dental, transdermal and intranasal delivery systems. Different formulations of DDS are also overviewed in this review article along with synthesis techniques employed for designing the DDS. The possibility of these biopolymer applications points to a new route for creating unique DDS with enhanced therapeutic qualities for scaling up creative formulations up to the clinical level.

Association of serum leptin and resistin levels among obese Saudi patients with acute myocardial infarction in Asir region.

In the current scenario, the importance of cardiac biomarkers in diagnosing, assessing, and managing people with cardiovascular discomfort is required. This cross-sectional study examined the relationship between serum leptin and resistin levels among obese people with acute myocardial infarction (AMI) with varying body mass index (BMI). The cardio and diabetic biomarkers among the 77 Saudi patients with hypoxia who lived in the Asir region were analyzed in the study. The patients were categorized into three groups, namely, group 1 (control), group 2 (AMI with normal BMI), and group 3 (AMI with varying BMI). Our results showed a positive correlation between serum glucose, HbA1C, triglycerides, Troponin-I (cTnI), creatine kinase MB (CK-MB), leptin, and resistin in patients with AMI. We also observed significantly lower HbA1C, cholesterol, and insulin values in groups 2 and 3. A statistical difference between the groups with and without AMI and between the genders was noticed. BMI with leptin showed a positive connection in group 3 but no association was observed for groups 1 and 2. A stronger relationship between BMI and leptin levels in men in Group 3 than in women was observed. In all three groups, resistin levels did not correlate with BMI. Thus, circulating leptin concentrations do not significant impact AMI compared to participants with and without AMI. However, resistin levels were considerably higher in obese individuals with AMI. Therefore, we suggest that resistin can be used as a pro-inflammatory marker to detect AMI disorder with varying BMI and as a prognostic marker associated with AMI.

Bone morphogenetic protein (BMP)9 in cancer development: mechanistic, diagnostic, and therapeutic approaches?

Bone morphogenetic protein (BMP)-9 is considered a member of the transforming growth factor (TGF)ß superfamily. It was first found as an inducer of bone and cartilage formation and then discovered that this factor mediates several physiologic functions and hemostasis. Besides physiological conditions, BMP9 has also been elucidated that it is involved in several pathological situations, especially cancer. In various cancers, dysregulation of BMP9 has raised the issue that BMP9 might play a conflicting role in tumour development. BMP9 binding to its receptors (BMPRs), including ALKs and BMPRII, induces canonical SMAD-dependent and non-canonical PI3K/AKT and MAPK signalling pathways in tumour cells. BMP9, via inducing apoptosis, inhibiting tumour-promoting cell signalling pathways, suppressing epithelial-mesenchymal transition (EMT) process, blocking angiogenesis, and preventing cross-talk in the tumour microenvironment, mainly exerts tumour-suppressive functions. In contrast, BMP9 triggers tumour-supportive signalling pathways, promotes EMT, and enhances angiogenesis, suggesting that BMP9 is also involved in tumour development. It has been demonstrated that modulating BMP9 expression and functions might be a promising approach to cancer treatment. It has also been indicated that evaluating BMP9 expression in cancers might be a biomarker for predicting cancer prognosis. Overall, BMP9 would provide a promising target in cancer management.

Identification of Potent Inhibitors Targeting EGFR and HER3 for Effective Treatment of Chemoresistance in Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Despite the existence of various therapeutic options, NSCLC is still a major health concern due to its aggressive nature and high mutation rate. Consequently, HER3 has been selected as a target protein along with EGFR because of its limited tyrosine kinase activity and ability to activate PI3/AKT pathway responsible for therapy failure. We herein used a BioSolveIT suite to identify potent inhibitors of EGFR and HER3. The schematic process involves screening of databases for constructing compound library comprising of 903 synthetic compounds (602 for EGFR and 301 for HER3) followed by pharmacophore modeling. The best docked poses of compounds with the druggable binding site of respective proteins were selected according to pharmacophore designed by SeeSAR version 12.1.0. Subsequently, preclinical analysis was performed via an online server SwissADME and potent inhibitors were selected. Compound 4k and 4m were the most potent inhibitors of EGFR while 7x effectively inhibited the binding site of HER3. The binding energies of 4k, 4m, and 7x were -7.7, -6.3 and -5.7 kcal/mol, respectively. Collectively, 4k, 4m and 7x showed favorable interactions with the most druggable binding sites of their respective proteins. Finally, in silico pre-clinical testing by SwissADME validated the non-toxic nature of compounds 4k, 4m and 7x providing a promising treatment option for chemoresistant NSCLC.

Synthesis, in vitro biological assessment, and molecular docking study of benzimidazole-based thiadiazole derivatives as dual inhibitors of α-amylase and α-glucosidase.

The clinical significance of benzimidazole-containing drugs has increased in the current study, making them more effective scaffolds. These moieties have attracted strong research interest due to their diverse biological features. To examine their various biological significances, several research synthetic methodologies have recently been established for the synthesis of benzimidazole analogs. The present study aimed to efficiently and quickly synthesize a new series of benzimidazole analogs. Numerous spectroscopic techniques, including 1H-NMR, 13C-NMR, and HREI-MS, were used to confirm the synthesized compounds. To explore the inhibitory activity of the analogs against α-amylase and α-glucosidase, all derivatives (1-17) were assessed for their biological potential. Compared to the reference drug acarbose (IC50 = 8.24 ± 0.08 µM), almost all the derivatives showed promising activity. Among the tested series, analog 2 (IC50 = 1.10 ± 0.10 & 2.10 ± 0.10 µM, respectively) displayed better inhibitory activity. Following a thorough examination of the various substitution effects on the inhibitory capacity of α-amylase and α-glucosidase, the structure-activity relationship (SAR) was determined. We looked at the potential mechanism of how active substances interact with the catalytic cavity of the targeted enzymes in response to the experimental results of the anti-glucosidase and anti-amylase. Molecular docking provided us with information on the interactions that the active substances had with the various amino acid residues of the targeted enzymes for this purpose.

Identification of Potential Inhibitors for the Treatment of Alkaptonuria Using an Integrated In Silico Computational Strategy.

Alkaptonuria (AKU) is a rare genetic autosomal recessive disorder characterized by elevated serum levels of homogentisic acid (HGA). In this disease, tyrosine metabolism is interrupted because of the alterations in homogentisate dioxygenase (HGD) gene. The patient suffers from ochronosis, fractures, and tendon ruptures. To date, no medicine has been approved for the treatment of AKU. However, physiotherapy and strong painkillers are administered to help mitigate the condition. Recently, nitisinone, an FDA-approved drug for type 1 tyrosinemia, has been given to AKU patients in some countries and has shown encouraging results in reducing the disease progression. However, this drug is not the targeted treatment for AKU, and causes keratopathy. Therefore, the foremost aim of this study is the identification of potent and druggable inhibitors of AKU with no or minimal side effects by targeting 4-hydroxyphenylpyruvate dioxygenase. To achieve our goal, we have performed computational modelling using BioSolveIT suit. The library of ligands for molecular docking was acquired by fragment replacement of reference molecules by ReCore. Subsequently, the hits were screened on the basis of estimated affinities, and their pharmacokinetic properties were evaluated using SwissADME. Afterward, the interactions between target and ligands were investigated using Discovery Studio. Ultimately, compounds c and f were identified as potent inhibitors of 4-hydroxyphenylpyruvate dioxygenase.

Antibacterial and Antibiofilm Activities of ß-Lapachone by Modulating the Catalase Enzyme.

BACKGROUND: Bacterial infections constantly have a large impact on public health, because of increased rates of resistance and reduced frequency of development of novel antibiotics. The utility of conventional antibiotics for treating bacterial infections has become increasingly challenging. The aim of the study was to assess the antibacterial effect of ß-Lapachone (ß-Lap), a novel synthetic compound. METHODS: The antibacterial activity of the ß-Lap compound was examined against laboratory strains by agar well diffusion method and broth dilution assay. Growth kinetics in presence of ß-Lap on Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa (ATCC 27853) were assessed by microplate alamarBlue assay. Crystal violet blue assay was used for biofilm inhibition and biofilm eradication. P. aeruginosa catalase (KatA) complexed with ß-Lap was modeled using molecular docking approach. RESULTS: ß-Lap exhibited potent antimicrobial activity against laboratory strains of bacteria with MIC of 0.2 mM for S. saprophyticus and Staphylococcus aureus, and 0.04 mM for Staphylococcus epidermidis and Pseudomonas aeruginosa ATCC 27853. The inhibition of catalase enzyme was found to be the cause for its antibacterial activity. Bioinformatics analysis suggests that ß-Lap can inhibit KatA activity by interacting with catalase proximal active site and heme binding site. The activity of some commercial antibiotics was enhanced in association with ß-Lap. In addition, ß-Lap inhibited the biofilm formation and eradicated the already formed and ultra-mature biofilms of aforesaid bacterial strains. CONCLUSION: These observations indicated that ß-Lap could be a promising antibacterial agent for the treatment and prevention of infectious diseases.

Ultrasound-Assisted Synthesis of Piperidinyl-Quinoline Acylhydrazones as New Anti-Alzheimer's Agents: Assessment of Cholinesterase Inhibitory Profile, Molecular Docking Analysis, and Drug-like Properties.

Alzheimer's disease (AD) is one of the progressive neurological disorders and the main cause of dementia all over the world. The multifactorial nature of Alzheimer's disease is a reason for the lack of effective drugs as well as a basis for the development of new structural leads. In addition, the appalling side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with the marketed treatment modalities and many failed clinical trials significantly limit the use of drugs and alarm for a detailed understanding of disease heterogeneity and the development of preventive and multifaceted remedial approach desperately. With this motivation, we herein report a diverse series of piperidinyl-quinoline acylhydrazone therapeutics as selective as well as potent inhibitors of cholinesterase enzymes. Ultrasound-assisted conjugation of 6/8-methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes (4a,b) and (un)substituted aromatic acid hydrazides (7a-m) provided facile access to target compounds (8a-m and 9a-j) in 4-6 min in excellent yields. The structures were fully established using spectroscopic techniques such as FTIR, 1H- and 13C NMR, and purity was estimated using elemental analysis. The synthesized compounds were investigated for their cholinesterase inhibitory potential. In vitro enzymatic studies revealed potent and selective inhibitors of AChE and BuChE. Compound 8c showed remarkable results and emerged as a lead candidate for the inhibition of AChE with an IC50 value of 5.3 ± 0.51 µM. The inhibitory strength of the optimal compound was 3-fold higher compared to neostigmine (IC50 = 16.3 ± 1.12 µM). Compound 8g exhibited the highest potency and inhibited the BuChE selectively with an IC50 value of 1.31 ± 0.05 µM. Several compounds, such as 8a-c, also displayed dual inhibitory strength, and acquired data were superior to the standard drugs. In vitro results were further supported by molecular docking analysis, where potent compounds revealed various important interactions with the key amino acid residues in the active site of both enzymes. Molecular dynamics simulation data, as well as physicochemical properties of the lead compounds, supported the identified class of hybrid compounds as a promising avenue for the discovery and development of new molecules for multifactorial diseases, such as Alzheimer's disease (AD).

Designing multi-epitope monkeypox virus-specific vaccine using immunoinformatics approach.

BACKGROUND: Monkeypox virus is an enveloped DNA virus that belongs to Poxviridae family. The virus is transmitted from rodents to primates via infected body fluids, skin lesions, and respiratory droplets. After being infected with virus, the patients experience fever, myalgia, maculopapular rash, and fluid-filled blisters. It is necessary to differentiate monkeypox virus from other poxviruses during diagnosis which can be appropriately envisioned via DNA analysis from swab samples. During small outbreaks, the virus is treated with therapies administered in other orthopoxviruses infections and does not have its own specific therapy and vaccine. Consequently, in this article, two potential peptides have been designed. METHODS: For the purpose of designing a vaccine, protein sequences were retrieved followed by the prediction of B- and T-cell epitopes. Afterward, vaccine structures were predicted which were docked with toll-like receptors. The docked complexes were analyzed with iMODS. Moreover, vaccine constructs nucleotide sequences were optimized and expressed in silico. RESULTS: COP-B7R vaccine construct (V1) has antigenicity score of 0.5400, instability index of 29.33, z-score of - 2.11-, and 42.11% GC content whereas COP-A44L vaccine construct (V2) has an antigenicity score of 0.7784, instability index of 23.33, z-score of - 0.61, and 48.63% GC content. It was also observed that COP-A44L can be expressed as a soluble protein in Escherichia coli as compared to COP-B7R which requires a different expression system. CONCLUSION: The obtained results revealed that both vaccine constructs show satisfactory outcomes after in silico investigation and have significant potential to prevent the monkeypox virus. However, COP-A44L gave better results.

Computational approaches for innovative anti-viral drug discovery using Orthosiphon aristatus blume miq against dengue virus.

Dengue virus has emerged as infectious mosquito borne disease involved in lowering platelets and white blood cells (WBC) count particularly. The genome structure is based on several structural and non-structural proteins essential for viral replication and progeny. One of the major proteins of replication is non-structural protein 3 (NS3) that transforms polyproteins into functional proteins with a cofactor non-structural protein (NS2B). Heat Shock Protein 70 (HSP70), is a human protein that assists in replication, viral entry and virion synthesis. Therefore, to inhibit the spread of dengue infection, there is a need of antivirals targeting replication proteins and other human proteins that help in dengue virus multiplication. By systemic approach based on molecular docking, ADMET (absorption, distribution, metabolism, excretion and toxicity) properties and molecular dynamic simulation (MD), potent inhibitors can be predicted. Inhibition of NS2B/NS3 dengue and HSP70 proteins involved in multiple steps in dengue virus progression can be prevented by using different phytochemicals. Molecular docking was performed using AutoDock Vina, PatchDock, and SwissDock. Interactions of obtained complex were observed in PyMOL and PLIP. Validation was checked by PROCHEK, simulation was performed using iMODS followed by preclinical testing by admetSAR. Ladanein, a flavonoid of Orthosiphon aristatus, was obtained as the lead compound to inhibit major replication protein of dengue virus with inhibitory potential against HSP70 protein. In summary, various in silico approaches were used to obtain the best phytochemical having anti-dengue potential.Communicated by Ramaswamy H. Sarma.

High-throughput computational screening and in vitro evaluation identifies 5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl) phenyl]-1H-isoindole-1,3(2H)-dione (C3), as a novel EGFR-HER2 dual inhibitor in gastric tumors.

Gastric cancers are caused primarily due to the activation and amplification of the EGFR or HER2 kinases resulting in cell proliferation, adhesion, angiogenesis, and metastasis. Conventional therapies are ineffective due to the intra-tumoral heterogeneity and concomitant genetic mutations. Hence, dual inhibition strategies are recommended to increase potency and reduce cytotoxicity. In this study, we have conducted computational high-throughput screening of the ChemBridge library followed by in vitro assays and identified novel selective inhibitors that have a dual impediment of EGFR/HER2 kinase activities. Diversity-based High-throughput Virtual Screening (D-HTVS) was used to screen the whole ChemBridge small molecular library against EGFR and HER2. The atomistic molecular dynamic simulation was conducted to understand the dynamics and stability of the protein-ligand complexes. EGFR/HER2 kinase enzymes, KATOIII, and Snu-5 cells were used for in vitro validations. The atomistic Molecular Dynamics simulations followed by solvent-based Gibbs binding free energy calculation of top molecules, identified compound C3 (5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl) phenyl]-1H-isoindole-1,3(2H)-dione) to have a good affinity for both EGFR and HER2. The predicted compound, C3, was promising with better binding energy, good binding pose, and optimum interactions with the EGFR and HER2 residues. C3 inhibited EGFR and HER2 kinases with IC50 values of 37.24 and 45.83 nM, respectively. The GI50 values of C3 to inhibit KATOIII and Snu-5 cells were 84.76 and 48.26 nM, respectively. Based on these findings, we conclude that the identified compound C3 showed a conceivable dual inhibitory activity on EGFR/HER2 kinase, and therefore can be considered as a plausible lead-like molecule for treating gastric cancers with minimal side effects, though testing in higher models with pharmacokinetic approach is required.

BV6 enhances apoptosis in Lung cancer cells by ameliorating caspase expressions through attenuation of XIAP, cIAP-1, and cIAP-2 proteins.

Objective: The present study aimed to investigate the inhibitory role of second mitochondria determined activator of caspases mimetic on inhibitor of apoptosis proteins (IAPs) and regulation of caspases in nonsmall cell lung cancer cell line. Materials and Methods: Dimethyl sulfoxide and 3-(4, 5-dimethyl thizol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay was done to determine the IC50 of BV6 using NCI-H23 cell line. The levels of mRNA of X-linked IAP (XIAP), cellular IAP (cIAP-1), cIAP-2, caspase-6, and caspase-7 in H23 cell line were evaluated by a quantitative real-time polymerase chain reaction, while their protein expressions were tested using western blotting. Results: Two doses of BV6 dependently downregulated the expression of mRNA of XIAP (P = 0.002, P= 0.0003 vs. untreated), cIAP-1 (P = 0.05, P = 0.005 vs. untreated), and cIAP-2 (P = 0.001, P = 0.0002 vs. untreated), respectively, while the compound upregulated the mRNA expression of caspase-6 (P = 0.001, P < 0.0001 vs. untreated) and caspase-7 (P = 0.001, P = 0.0004 vs. untreated), respectively. Dose dependent of BV6 treatment significantly decreased the protein level of XIAP (P = 0.003, P = 0.007 vs. untreated), cIAP-1 (P = 0.02, P = 0.01 vs. untreated), and cIAP-2 (P = 0.008,P = 0.008 vs. untreated), respectively. However, the compound increased the protein level of caspase-6 and caspase-7 when compared to untreated control (P = 0.006,P = 0.001) and (P = 0.01, P = 0.001), respectively. Conclusions: The result showed that BV6 treatment reduced the level of mRNA of XIAP, cIAP-1, and cIAP-2 and increased the gene expression of caspase-6 and caspase-7 in NCI-H23 cell line. Therefore, the study revealed that BV6 could be used in future as additional therapeutics in lung cancer.

Synthesis, In Vitro Biological Evaluation and In Silico Molecular Docking Studies of Indole Based Thiadiazole Derivatives as Dual Inhibitor of Acetylcholinesterase and Butyrylchloinesterase.

The current study was conducted to obtain hybrid analogues of indole-based thiadiazole derivatives (1-16) in which a number of reaction steps were involved. To examine their biological activity in the presence of the reference drug Donepezil (0.21 ± 0.12 and 0.30 ± 0.32 M, respectively), the inhibitory potentials of AChE and BuChE were determined for these compounds. Different substituted derivatives showing a varied range of inhibitory profiles, when compared to the reference drug, analogue 8 was shown to have potent activity, with IC50 values for AchE 0.15 ± 0.050 M and BuChE 0.20 ± 0.10, respectively, while other substituted compounds displayed good to moderate potentials. Varied spectroscopic techniques including 1H, 13CNMR and HREI-MS were used to identify the basic skeleton of these compounds. Furthermore, all analogues have a known structure-activity relationship (SAR), and molecular docking investigations have verified the binding interactions of molecule to the active site of enzymes.

Antibacterial and anti-biofilm activity of plumbagin against multi-drug resistant clinical bacterial isolates.

OBJECTIVES: To evaluate the antibacterial activity of plumbagin (PGN) against multidrug resistance (MDR) clinical isolates. METHODS: This study was carried out at the Department of Clinical Lab Sciences, King Khalid University from October 6, 2021 to December 14, 2021. We investigated the antibacterial and anti-virulence activity of PGN against MDR Gram-negative (Escherichia coli, Klebsiella pneumoniae, Salmonella Typhi, and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus [S. aureus], Staphylococcus saprophyticus [S. saprophyticus], Streptococcus pyogenes, and Enterococcus faecalis) clinical bacterial isolates. Agar well diffusion, microdilution assay, colony count method, biofilm formation, and time-kill kinetics were employed to probe the MIC, MBC, and anti-virulence activity of PGN. RESULTS: Plumbagin inhibited the growth of all tested isolates, with S. saprophyticus exhibiting the highest sensitivity. MIC values ranged from 0.029 to 0.117 µg/mL whereas MBC ranged from 0.235 to 0.94 µg/mL, with 79% to 99% growth inhibition. Moreover, all tested isolates showed a marked decrease in biofilm formation, with S. saprophyticus and S. aureus being the most sensitive. CONCLUSION: Plumbagin is a stand-alone, broad spectrum antibacterial with promising potential against the rising threat of antimicrobial resistance.

Bioinformatics approach for the construction of multiple epitope vaccine against omicron variant of SARS-CoV-2.

The World Health Organization categorized SARS-CoV-2 as a variant of concern, having numerous mutations in spike protein, which have been found to evade the effect of antibodies stimulated by the COVID-19 vaccine. The susceptibility to omicron variant by immunization-induced antibodies are direly required for risk evaluation. To avoid the risk of arising viral illness, the construction of a specific vaccine that triggers the production of targeted antibodies to combat infection remains highly imperative. The aim of the present study is to develop a particular vaccine exploiting bioinformatics approaches which can target B- and T-cells epitopes. Through this approach, novel epitopes of the S protein-SARS-CoV-2 were predicted for the development of a multiple epitope vaccine. Multiple epitopes were selected on the basis of toxicity, immunogenicity and antigenicity, and vaccine subunit was constructed having potential immunogenic properties. The epitopes were linked with 3 types of linker EAAAK, AAY and GPGPG for vaccine construction. Subsequently, vaccine structure was docked with the receptor and cloned in a pET-28a (+) vector. The constructed vaccine was ligated in pET-28a (+) vector in E. coli using the SnapGene tool for the expression study and a good immune response was observed. Several computational tools were used to predict and analyze the vaccine constructed by using spike protein sequence of omicrons. The current study identified a Multi-Epitope Vaccine (MEV) as a significant vaccine candidate that could potentially help the global world to combat SARS-CoV-2 infections.

Comparative Evaluation of Various Extraction Techniques for Secondary Metabolites from Bombax ceiba L. Flowering Plants along with In Vitro Anti-Diabetic Performance.

Bombax ceiba L. (Family: Malvaceae) was rightly called the "silent doctor" in the past as every part of it had medicinal value. For centuries, humans have used this plant according to the traditional medicinal systems of China, Ayurveda, and tribal communities. Recently, with an emerging interest in herbals, attention has been paid to scientifically validating medicinal claims for the treatment of diabetes using secondary metabolites of B. ceiba L. flowers. In the present study, specific secondary metabolites from the flowers of B. ceiba L. were isolated in good yield using the solvent extraction methodology, and their in vitro anti-diabetic efficacy was examined. Extraction efficiency of each solvent for secondary metabolites was found in following order: water > ethanol> methanol > chloroform > petroleum ether. Quantitative analysis of secondary metabolites showed 120.33 ± 2.33 mg/gm polyphenols, 60.77 ± 1.02 mg/g flavonoids, 60.26 ± 1.20 mg/g glycosaponins, 0.167 ± 0.02 mg/g polysaccharides for water extract; 91.00 ± 1.00 mg/g polyphenols, 9.22 ± 1.02 mg/g flavonoids, 43.90 ± 0.30 mg/g glycosaponins, 0.090 ± 0.03 mg/g poly saccharides for ethanol extract; 52.00 ± 2.64 mg/g polyphenols, 35.22 ± 0.38 mg/g flavonoids, 72.26 ± 1.05 mg/g glycosaponins, 0.147 ± 0.01 mg/g polysaccharides for methanol extract; 11.33 ± 0.58 mg/g polyphenols, 23.66 ± 1.76 mg/g flavonoids, 32.8 ± 0.75 mg/g glycosaponins, 0.013 ± 0.02 mg/g polysaccharides for chloroform extract; and 3.33 ± 1.53 mg/g polyphenols, 1.89 ± 1.39 mg/g flavonoids, 21.67 ± 1.24 mg/g glycosaponins, 0.005 ± 0.01 mg/g polysaccharides for petroleum ether extract. Glucose uptake by yeast cells increased 70.38 ± 2.17% by water extract.

Fabrication of Cr-ZnFe2O4/S-g-C3N4 Heterojunction Enriched Charge Separation for Sunlight Responsive Photocatalytic Performance and Antibacterial Study.

There has been a lot of interest in the manufacture of stable, high-efficiency photocatalysts. In this study, initially Cr doped ZnFe2O4 nanoparticles (NPs) were made via surfactant-assisted hydrothermal technique. Then Cr-ZnFe2O4 NPs were modified by incorporating S-g-C3N4 to enhance their photocatalytic efficiency. The morphological, structural, and bonding aspects were analyzed by XRD, FTIR, and SEM techniques. The photocatalytic efficiency of the functional Cr-ZnFe2O4/S-g-C3N4 (ZFG) heterostructure photocatalysts was examined against MB under sunlight. The produced ZFG-50 composite has the best photocatalytic performance, which is 2.4 and 3.5 times better than that of ZnFe2O4 and S-g-C3N4, respectively. Experiments revealed that the enhanced photocatalytic activity of the ZFG nanocomposite was caused by a more effective transfer and separation of photo-induced charges. The ZFG photocatalyst can use sunlight for treating polluted water, and the proposed modification of ZnFe2O4 using Cr and S-g-C3N4 is efficient, affordable, and environmentally benign. Under visible light, Gram-positive and Gram-negative bacteria were employed to ZFG-50 NCs' antimicrobial activity. These ZFG-50 NCs also exhibit excellent antibacterial potential.

Synthesis of Novel Benzimidazole-Based Thiazole Derivatives as Multipotent Inhibitors of α-Amylase and α-Glucosidase: In Vitro Evaluation along with Molecular Docking Study.

In this study, hybrid analogs of benzimidazole containing a thiazole moiety (1-17) were afforded and then tested for their ability to inhibit α-amylase and α-glucosidase when compared to acarbose as a standard drug. The recently available analogs showed a wide variety of inhibitory potentials that ranged between 1.31 ± 0.05 and 38.60 ± 0.70 µM (against α-amylase) and between 2.71 ± 0.10 and 42.31 ± 0.70 µM (against α-glucosidase) under the positive control of acarbose (IC50 = 10.30 ± 0.20 µM against α-amylase) (IC50 = 9.80 ± 0.20 µM against α-glucosidase). A structure-activity relationship (SAR) study was carried out for all analogs based on substitution patterns around both rings B and C respectively. It was concluded from the SAR study that analogs bearing either substituent(s) of smaller size (-F and Cl) or substituent(s) capable of forming hydrogen bonding (-OH) with the catalytic residues of targeted enzymes enhanced the inhibitory potentials. Therefore, analogs 2 (bearing meta-fluoro substitution), 3 (having para-fluoro substitution) and 4 (with ortho-fluoro group) showed enhanced potency when evaluated against standard acarbose drug with IC50 values of 4.10 ± 0.10, 1.30 ± 0.05 and 1.90 ± 0.10 (against α-amylase) and 5.60 ± 0.10, 2.70 ± 0.10 and 2.90 ± 0.10 µM (against α-glucosidase), correspondingly. On the other hand, analogs bearing substituent(s) of either a bulky nature (-Br) or that are incapable of forming hydrogen bonds (-CH3) were found to lower the inhibitory potentials. In order to investigate the binding sites for synthetic analogs and how they interact with the active areas of both targeted enzymes, molecular docking studies were also conducted on the potent analogs. The results showed that these analogs adopted many important interactions with the active areas of enzymes. The precise structure of the newly synthesized compounds was confirmed using several spectroscopic techniques as NMR and HREI-MS.