Muhammad Saad Khan

Curcumin has been used in traditional medicine forages. The present study aimed to develop a curcumin-based hydrogel system and assess its antimicrobial potential and wound healing (WH) activity on an invitro and in silico basis. A topical hydrogel was prepared using chitosan, PVA, and Curcumin in varied ratios, and hydrogels were evaluated for physicochemical properties. The hydrogel showed antimicrobial activity against both gram-positive and gram-negative microorganisms. In silico studies showed good binding energy scores and significant interaction of curcumin components with key residues of inflammatory proteins that help in WH activity. Dissolution studies showed sustained release of curcumin. Overall, the results indicated wound healing potential of chitosan–PVA–curcumin hydrogel films. Further in vivo experiments are needed to evaluate the clinical efficacy of such films for wound healing.

Phytochemicals have been shown to possess multiple bioactives and have been reported to showcase many medicinal effects. A similar kind of evaluation of phytoconstituents for their antimicrobial action has been reported, based on in vitro and in silico data. The goal of the research was to explore bioactive phytoconstituents of Eclipta alba leaf for antimicrobial activity. The antimicrobial activity was validated by both molecular docking and antimicrobial assay. Bioactive metabolites were identified using GC-MS. The antimicrobial and antimycobacterial activity of Eclipta alba leaves was investigated using the KirbyBauer well diffusion method and the rapid cultureMGIT DST method against a variety of human pathogens, as well as Mycobacterium tuberculosis (H37Rv) and Mycobacterium tuberculosis bacteria resistant to isoniazid and rifampicin. Eclipta alba’s GC-MS studies confirmed the detection of 17 bioactive constituents. The extract demonstrates the highest antibacterial activity against Escherichia coli (sensitive), Pseudomonas aeruginosa (sensitive) and methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa susceptible and MRSA (sensitive) with zone of inhibition of 27mm, 24mm, and 32mm respectively. The extract showed no effect on Mycobacterium tuberculosis (H37Rv) and Mycobacterium tuberculosis bacteria resistant to isoniazid and rifampicin in antimycobacterial activity testing. Molecular docking investigation revealed that three compounds (phthalic acid, isobutyl octadecyl ester, hexadecanoic acid, 1(hydroxymethyl)1,2-ethanediylester, and 2,myristynoyl pantetheine) have generated the best results in terms of binding energies and significant interactions with key residues of target protein 3-hydroxydecanoyl-acyl carrier protein dehydratase (FabA) and confirm its activity as antimicrobial inhibitors. These two-dimensional plots show significant protein-ligand binding interactions (van der Waals interactions, hydrogen bond, alkyl, and Pi-alkyl interactions). ADMET (absorption, distribution, metabolism, excretion, and toxicity) results additionally support the drug-likeness characteristics of concluded potential compounds. The experimental and computational results demonstrated that methanolic extract of Eclipta alba leaves had antimicrobial effects for specific infections due to the presence of phytochemical compounds.

Phytopathogenic fungi are serious threats in the agriculture sector especially in fruit and vegetable production. The use of plant essential oil as antifungal agents has been in practice from many years. Plant essential oils (PEOs) of Cuminum cyminum, Trachyspermum ammi, Azadirachta indica, Syzygium aromaticum, Moringa oleifera, Mentha spicata, Eucalyptus grandis, Allium sativum, and Citrus sinensis were tested against Fusarium oxysporum. Three phase trials consist of lab testing (MIC and MFC), field testing (seed treatment and foliar spray), and computer‐aided fungicide design (CAFD). Two concentrations (25 and 50 μl/ml) have been used to asses MIC while MFC was assessed at four concentrations (25, 50, 75, and 100 μl/ml). C. sinensis showed the largest inhibition zone (47.5 and 46.3 m²) for both concentrations. The lowest disease incidence and disease severity were recorded in treatments with C. sinensis PEO. Citrus sinensis that qualified in laboratory and field trials was selected for CAFD. The chemical compounds of C. sinensis PEO were docked with polyketide synthase beta‐ketoacyl synthase domain of F. oxysporum by AutoDock Vina. The best docked complex was formed by nootkatone with ‐6.0 kcal/mol binding affinity. Pharmacophore of the top seven C. sinensis PEO compounds was used for merged pharmacophore generation. The best pharmacophore model with 0.8492 score was screened against the CMNP database. Top hit compounds from screening were selected and docked with polyketide synthase beta‐ketoacyl synthase domain. Four compounds with the highest binding affinity and hydrogen bonding were selected for confirmation of lead molecule by doing MD simulation. The polyketide synthase‐CMNPD24498 showed the highest stability throughout 80 ns run of MD simulation. CMNPD24498 (FW054‐1) from Verrucosispora was selected as the lead compound against F. oxysporum.

Diabetes mellitus (DM) is a very common metabolic disorder/disease. The deterioration of β-cells by autoimmune system is the hallmark of this disease. Thioredoxin-Interacting Protein (TXNIP) is responsible for β-cells degradation by T-cells in the pancreas. This protein had been declared a good drug target for controlling DM. Lots of side effects have been reported as a result of long-time consumption of conventional antidiabetic drugs. The development of new and effective drugs with the minimal side effects needs time. TXNIP was selected as a target for Computer-Aided Drug Design. The antidiabetic fungal metabolite compounds were selected from the literature. The compounds were screened for their drug-likeness properties by DruLiTo and DataWarior tools. Twenty-two drug-like fungal compounds were subjected to Quantitative Structure-Activity Relationship (QSAR) analysis by using CheS-Mapper 2.0. The lowest (0.01) activity cliff was found for three compounds: Pinazaphilone A, Pinazaphilone B, and Chermesinone A. The highest value for apol (81.76) was shown by Asperphenamate, while Albonoursin and Sterenin L showed highest score (40.66) for bpol. The lowest value (0.46) for fractional molecular frame (FMF) was calculated for Pinazaphilone A and Pinazaphilone B. TPSA for Pinazaphilone A and Pinazaphilone B was 130.51 Ų. was observed for all the twenty-two compounds. Molecular docking of fungal compounds with TXNIP was done by AutoDock Vina. The binding energy for complexes ranged between −9.2 and −4.6 kcal/mol. Four complexes, TXNIP-Pinazaphilone A, TXNIP-Pinazaphilone B, TXNIP-Asperphenamate, and TXNIP-Sterenin L, were selected for MD simulation to find out the best lead molecule. Only one complex, TXNIP-Pinazaphilone B, showed a stable conformation throughout the 80 ns run of MD simulation. Pinazaphilone B derived from the Penicillium species fungi was selected as the lead molecule for development of antidiabetic drug having the least side effects.

In the present study, chitosan/polyvinyl alcohol (PVA)-based honey hydrogel films were developed for potential wound healing application. The hydrogel films were developed by a solvent-casting method and were evaluated in terms of thickness, weight variation, folding endurance, moisture content and moisture uptake. The water vapor transmission rate was found to range between 1650.50 ± 35.86 and 2698.65 ± 76.29 g/m²/day. The tensile strength and elongation at break were found to range between 4.74 ± 0.83 and 38.36 ± 5.39 N, and 30.58 ± 3.64 and 33.51 ± 2.47 mm, respectively, indicating significant mechanical properties of the films. SEM images indicated smooth surface morphology of the films. FTIR, DSC and in silico analysis were performed, which highlighted the docking energies of the protein–ligand complex and binding interactions such as hydrogen bonding, Pi–Pi bonding, and Pi–H bonding between the selected compounds and target proteins; hence, we concluded, with the three best molecules (lumichrome, galagin and chitosan), that there was wound healing potential. In vitro studies pointed toward a sustained release of honey from the films. The antimicrobial performance of the films was investigated against Staphylococcus aureus. Overall, the results signaled the potential application of chitosan/PVA based hydrogel films as wound dressings. Furthermore, in vivo experiments may be required to evaluate the clinical efficacy of honey-loaded chitosan/PVA hydrogel films in wound healing.

Klebsiella oxytoca is a gram-negative bacterium. It is opportunistic in nature and causes hospital acquired infections. Subtractive proteomics and reverse vaccinology approaches were employed to screen out the best proteins for vaccine designing. Whole proteome of K. oxytoca strain ATCC 8724, consisting of 5483 proteins, was used for designing the vaccine. Total 1670 cytotoxic T lymphocyte (CTL) epitope were predicted through NetCTL while 1270 helper T lymphocyte (HTL) epitopes were predicted through IEDB server. The epitopes were screened for non-toxicity, allergenicity, antigenicity and water solubility. After epitope screening 300 CTL and 250 HTL epitopes were submitted to IFN-γ epitope server to predict their Interferon-γ induction response. The selected IFN-γ positive epitopes were tested for their binding affinity with MHCI-DRB1 by MHCPred. The 15 CTL and 13 HTL epitopes were joined by linkers AAY and GPGPG respectively in vaccine construct. Chain C of Pam3CSK4 (PDB ID; 2Z7X) was linked to the vaccine construct as an adjuvant. A 450aa long vaccine construct was submitted to I-TASSER server for 3D structure prediction. Thirteen Linear B cells were predicted by ABCPred server and 10 sets of discontinues epitopes for 3D vaccine structure were predicted by DiscoTope server. The modeled 3D vaccine construct was docked with human Toll-like receptor 2 (PDB ID: 6NIG) by PatchDock. The docked complexes were refined by FireDock. The selected docked complex showed five hydrogen bonds and one salt bridge. The vaccine sequence was reverse transcribed to get nucleotide sequence for In silico cloning. The reverse transcribed sequence strand was cloned in pET28a(+) expression vector. A clone containing 6586 bp was constructed including the 450 bp of query gene sequence.

Background: ATP-binding cassette Super-family G member 2 protein is an active ATPbinding cassette transporter with the potential to combat cancer stem cells.Objective: Due to the lack of potential ATP-binding cassette Super-family G member 2 inhibitors, we screened natural inhibitors, which could be a safe source to control multidrug resistance by blocking the regulation of ATP-binding cassette Super-family G member 2 protein.Methods: Three-dimensional structure of ATP-binding cassette Super-family G member 2 protein downloaded from the protein databank and chemical structures of 166 selected compounds of the training dataset were retrieved from PubChem. Drug-likeness and docking analysis was conducted to shortlist the dataset for pharmacophore generation. LigandScout 4.1.5 used for pharmacophorebased screening of Zbc library of ZINC database and Autodock Vina were utilized for molecular docking against the predicted active pocket of the target protein to evaluate the potential association of protein and ligands. The physiochemical properties of novel compounds were calculated by admetSAR respectively.Results: Through pharmacophore-based screening, ZINC4098704 (Rhein) was identified as a lead compound which demonstrates the least binding energy (-8.5) and the highest binding affinity with the target protein and showed optimal physiochemical profile. This compound is highly recommended for a laboratory test to confirm its activity as an ATP-binding cassette Super-family G member 2 inhibitors.Conclusion: Our computer-based study systematically selected natural lead compounds, which could be effective in inhibiting ATP-binding cassette Super-family G member 2 and may help reverse the effect of multidrug resistance to increase the effectiveness of chemotherapy in cancer treatment.

Sumoylation is the Post-translational modification gaining most of the research interest recently. Sumoylation is involved in various crucial functions of the cell such as regulation of cell cycle, DNA damage repair, apoptosis, etc. Oncology is advancing in radiotherapy, targeted chemotherapy, various forms of immunotherapy and targeted gene therapy. Researches are being conducted to prove its connotation with a variety of cancers and inhibitors are being developed to obstruct the fatal effect caused by misbalance of the SUMO-catalytic cycle. It has been shown that up-regulation of certain enzymes of Sumoylation correlates with cancer incidence in most of the cases. However, in some cases, down-regulation also associates with cancer invasion such as underexpression of UBC9 in initial stage breast cancer. This can aid in future study, treatment, and diagnosis of a variety of cancers including breast cancer, prostate cancer, lung adenocarcinoma, melanoma, multiple myeloma, etc. Various mechanistic assays are being developed and used to identify potential inhibitors against the dysregulated proteins of Sumoylation. This review summarizes the normal roles of the enzymes involved in the SUMOcatalytic cycle, their misbalanced regulation leading to tumorigenesis and nearly all the potent inhibitors identified to date, while after detailed studied it was observed that ML-792 could be a promising inhibitor in treating cancers by inhibiting Sumoylation enzymes.