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  1. Smart and pH-sensitive rGO/Arabinoxylan/chitosan composite for wound dressing: In-vitro drug delivery, antibacterial activity, and biological activities
    Khan MUA, Haider S, Raza MA, Shah SA, Razak SIA, Kadir MRA, et al.
    Int J Biol Macromol, 2021 Dec 01;192:820-831.
    PMID: 34648803 DOI: 10.1016/j.ijbiomac.2021.10.033
    Carbohydrate polymers are biological macromolecules that have sparked a lot of interest in wound healing due to their outstanding antibacterial properties and sustained drug release. Arabinoxylan (ARX), Chitosan (CS), and reduced graphene oxide (rGO) sheets were combined and crosslinked using tetraethyl orthosilicate (TEOS) as a crosslinker to fabricate composite hydrogels and assess their potential in wound dressing for skin wound healing. Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), atomic force microscopy (AFM), transmission electron microscopy (TEM), and biological assays were used to evaluate the composite hydrogels. FTIR validated the effective fabrication of the composite hydrogels. The rough morphologies of the composite hydrogels were revealed by SEM and AFM (as evident from the Ra values). ATC-4 was discovered to have the roughest surface. TEM revealed strong homogeneous anchoring of the rGO to the polymer matrix. However, with higher amount of rGO agglomeration was detected. The % swelling at various pHs (1-13) revealed that the hydrogels were pH-sensitive. The controlled release profile for the antibacterial drug (Silver sulfadiazine) evaluated at various pH values (4.5, 6.8, and 7.4) in PBS solution and 37 °C using the Franz diffusion method revealed maximal drug release at pH 7.4 and 37 °C. The antibacterial efficacy of the composite hydrogels against pathogens that cause serious skin diseases varied. The MC3T3-E1 cell adhered, proliferated, and differentiated well on the composite hydrogels. MC3T3-E1 cell also illustrated excellent viability (91%) and proper cylindrical morphologies on the composite hydrogels. Hence, the composite hydrogels based on ARX, CS, and rGO are promising biomaterials for treating and caring for skin wounds.
  2. Fulltext An IoMT-Enabled Smart Healthcare Model to Monitor Elderly People Using Machine Learning Technique
    Khan MF, Ghazal TM, Said RA, Fatima A, Abbas S, Khan MA, et al.
    Comput Intell Neurosci, 2021;2021:2487759.
    PMID: 34868288 DOI: 10.1155/2021/2487759
    The Internet of Medical Things (IoMT) enables digital devices to gather, infer, and broadcast health data via the cloud platform. The phenomenal growth of the IoMT is fueled by many factors, including the widespread and growing availability of wearables and the ever-decreasing cost of sensor-based technology. The cost of related healthcare will rise as the global population of elderly people grows in parallel with an overall life expectancy that demands affordable healthcare services, solutions, and developments. IoMT may bring revolution in the medical sciences in terms of the quality of healthcare of elderly people while entangled with machine learning (ML) algorithms. The effectiveness of the smart healthcare (SHC) model to monitor elderly people was observed by performing tests on IoMT datasets. For evaluation, the precision, recall, fscore, accuracy, and ROC values are computed. The authors also compare the results of the SHC model with different conventional popular ML techniques, e.g., support vector machine (SVM), K-nearest neighbor (KNN), and decision tree (DT), to analyze the effectiveness of the result.
  3. Semicarbazones, thiosemicarbazone, thiazole and oxazole analogues as monoamine oxidase inhibitors: Synthesis, characterization, biological evaluation, molecular docking, and kinetic studies
    Qazi SU, Naz A, Hameed A, Osra FA, Jalil S, Iqbal J, et al.
    Bioorg Chem, 2021 10;115:105209.
    PMID: 34364054 DOI: 10.1016/j.bioorg.2021.105209
    A series of semicarbazone, thiosemicarbazone, thiazole, and oxazole derivatives were designed, synthesized, and examined for monoamine oxidase inhibition using two isoforms, i.e., MAO-A and MAO-B. Among all the analogues, 3c and 3j possessed substantial activity against MAO-A with IC50 values of 5.619 ± 1.04 µM and 0.5781 ± 0.1674 µM, respectively. Whereas 3d and 3j were active against monoamine oxidase B with the IC50 values of 9.952 ± 1.831 µM and 3.5 ± 0.7 µM, respectively. Other derivatives active against MAO-B were 3c and 3g with the IC50 values of 17.67 ± 5.6 µM and 37.18 ± 2.485 µM. Moreover, molecular docking studies were achieved for the most potent compound (3j) contrary to human MAO-A and MAO-B. Kinetic studies were also performed for the most potent analogue to evaluate its mode of interaction with MAO-A and MAO-B.
  4. Synthesis, enzyme inhibition and molecular docking studies of 1-Arylsulfonyl-4-phenylpiperazine derivatives
    Abbasi MA, Anwar A, Rehman A, Siddiqui SZ, Rubab K, Shah SAA, et al.
    Pak J Pharm Sci, 2017 Sep;30(5):1715-1724.
    PMID: 29084694
    Heterocyclic molecules have been frequently investigated to possess various biological activities during the last few decades. The present work elaborates the synthesis and enzymatic inhibition potentials of a series of sulfonamides. A series of 1-arylsulfonyl-4-Phenylpiperazine (3a-n) geared up by the reaction of 1-phenylpiperazine (1) and different (un)substituted alkyl/arylsulfonyl chlorides (2a-n), under defined pH control using water as a reaction medium. The synthesized molecules were characterized by 1H-NMR, 13C-NMR, IR and EI-MS spectral data. The enzyme inhibition study was carried on α-glucosidase, lipoxygenase (LOX), acetyl cholinesterase (AChE) and butyryl cholinesterase (BChE) enzymes supported by docking simulation studies and the IC50 values rendered a few of the synthesized molecules as moderate inhibitors of these enzymes where, the compound 3e exhibited comparatively better potency against α-glucosidase enzyme. The synthesized compounds showed weak or no inhibition against LOX, AChE and BChE enzymes.
  5. Synthesis and in vitro study of benzofuran hydrazone derivatives as novel alpha-amylase inhibitor
    Taha M, Shah SAA, Imran S, Afifi M, Chigurupati S, Selvaraj M, et al.
    Bioorg Chem, 2017 12;75:78-85.
    PMID: 28918064 DOI: 10.1016/j.bioorg.2017.09.002
    The α-amylase acts as attractive target to treat type-2 diabetes mellitus. Therefore in discovering a small molecule as α-amylase inhibitor, we have synthesized benzofuran carbohydrazide analogs (1-25), characterized through different spectroscopic techniques such as 1HNMR and EI-MS. All screened analog shows good α-amylase inhibitory potentials with IC50 value ranging between 1.078±0.19 and 2.926±0.05µM when compared with acarbose having IC50=0.62±0.22µM. Only nine analogs among the series such as analogs 3, 5, 7, 8, 10, 12, 21, 23 and 24 exhibit good inhibitory potential with IC50 values 1.644±0.128, 1.078±0.19, 1.245±0.25, 1.843±0.19, 1.350±0.24, 1.629±0.015, 1.353±0.232, 1.359±0.119 and 1.488±0.07µM when compare with standard drug acarbose. All other analogs showed good to moderate α-amylase inhibitory potentials. The SAR study was conducted on the basis of substituent difference at the phenyl ring. The binding interaction between analogs and active site of enzyme was confirmed by docking studies.
  6. Synthesis, molecular docking study and in vitro thymidine phosphorylase inhibitory potential of oxadiazole derivatives
    Ullah H, Rahim F, Taha M, Uddin I, Wadood A, Shah SAA, et al.
    Bioorg Chem, 2018 08;78:58-67.
    PMID: 29533215 DOI: 10.1016/j.bioorg.2018.02.020
    We have synthesized oxadiazole derivatives (1-16), characterized by 1H NMR, 13C NMR and HREI-MS and screened for thymidine phosphorylase inhibitory potential. All derivatives display varied degree of thymidine phosphorylase inhibition in the range of 1.10 ± 0.05 to 49.60 ± 1.30 μM when compared with the standard inhibitor 7-Deazaxanthine having an IC50 value 38.68 ± 1.12 μM. Structure activity relationships (SAR) has been established for all compounds to explore the role of substitution and nature of functional group attached to the phenyl ring which applies imperious effect on thymidine phosphorylase activity. Molecular docking study was performed to understand the binding interaction of the most active derivatives with enzyme active site.
  7. Fulltext Partial differential equations modeling of thermal transportation in Casson nanofluid flow with arrhenius activation energy and irreversibility processes
    Al Oweidi KF, Jamshed W, Goud BS, Ullah I, Usman, Mohamed Isa SSP, et al.
    Sci Rep, 2022 Nov 29;12(1):20597.
    PMID: 36446992 DOI: 10.1038/s41598-022-25010-x
    The formation of entropy in a mixed convection Casson nanofluid model with Arhenius activation energy is examined in this paper using magnetohydrodynamics (MHD). The expanding sheet, whose function of sheet velocity is nonlinear, confines the Casson nanofluid. The final equations, which are obtained from the first mathematical formulations, are solved using the MATLAB built-in solver bvp4c. Utilizing similarity conversion, ODEs are converted in their ultimate form. A number of graphs and tabulations are also provided to show the effects of important flow parameters on the results distribution. Slip parameter was shown to increase fluid temperature and decrease entropy formation. On the production of entropy, the Brinkman number and concentration gradient have opposing effects. In the presence of nanoparticles, the Eckert number effect's augmentation of fluid temperature is more significant. Furthermore, a satisfactory agreement is reached when the findings of the current study are compared to those of studies that have been published in the past.
  8. Fulltext Author Correction: Partial differential equations modeling of thermal transportation in Casson nanofluid flow with arrhenius activation energy and irreversibility processes
    Al Oweidi KF, Jamshed W, Goud BS, Ullah I, Usman, Mohamed Isa SSP, et al.
    Sci Rep, 2023 Jan 31;13(1):1754.
    PMID: 36720992 DOI: 10.1038/s41598-023-28885-6
  9. Fulltext Cost of Illness Analysis of Type 2 Diabetes Mellitus: The Findings from a Lower-Middle Income Country
    Butt MD, Ong SC, Wahab MU, Rasool MF, Saleem F, Hashmi A, et al.
    Int J Environ Res Public Health, 2022 Oct 02;19(19).
    PMID: 36231911 DOI: 10.3390/ijerph191912611
    BACKGROUND: Diabetes is a major chronic illness that negatively influences individuals and society. Therefore, this research aimed to analyze and evaluate the cost associated with diabetes management, specific to the Pakistani Type 2 diabetes population. Research scheme and methods: A survey randomly collected information and data from diabetes patients throughout Pakistan out-patient clinics. Direct and indirect costs were evaluated, and data were analyzed with descriptive and inferential statistics.

    RESULTS: An overall of 1839 diabetes patients participated in the study. The results have shown that direct and indirect costs are positively associated with the participants' socio-demographic characteristics, except for household income and educational status. The annual total cost of diabetes care was USD 740.1, amongst which the share of the direct cost was USD 646.7, and the indirect cost was USD 93.65. Most direct costs comprised medicine (USD 274.5) and hospitalization (USD 319.7). In contrast, the productivity loss of the patients had the highest contribution to the indirect cost (USD 81.36).

    CONCLUSION: This study showed that direct costs significantly contributed to diabetes's overall cost in Pakistan and overall diabetes management estimated to be 1.67% (USD 24.42 billion) of the country's total gross domestic product. The expense of medications and hospitalization mostly drove the direct cost. Additionally, patients' loss of productivity contributed significantly to the indirect cost. It is high time for healthcare policymakers to address this huge healthcare burden. It is time to develop a thorough diabetes management plan to be implemented nationwide.

  10. Plant-soil-microbe interactions in maintaining ecosystem stability and coordinated turnover under changing environmental conditions
    Aqeel M, Ran J, Hu W, Irshad MK, Dong L, Akram MA, et al.
    Chemosphere, 2023 Mar;318:137924.
    PMID: 36682633 DOI: 10.1016/j.chemosphere.2023.137924
    Ecosystem functions directly depend upon biophysical as well as biogeochemical reactions occurring at the soil-microbe-plant interface. Environment is considered as a major driver of any ecosystem and for the distributions of living organisms. Any changes in climate may potentially alter the composition of communities i.e., plants, soil microbes and the interactions between them. Since the impacts of global climate change are not short-term, it is indispensable to appraise its effects on different life forms including soil-microbe-plant interactions. This article highlights the crucial role that microbial communities play in interacting with plants under environmental disturbances, especially thermal and water stress. We reviewed that in response to the environmental changes, actions and reactions of plants and microbes vary markedly within an ecosystem. Changes in environment and climate like warming, CO2 elevation, and moisture deficiency impact plant and microbial performance, their diversity and ultimately community structure. Plant and soil feedbacks also affect interacting species and modify community composition. The interactive relationship between plants and soil microbes is critically important for structuring terrestrial ecosystems. The anticipated climate change is aggravating the living conditions for soil microbes and plants. The environmental insecurity and complications are not short-term and limited to any particular type of organism. We have appraised effects of climate change on the soil inhabiting microbes and plants in a broader prospect. This article highlights the unique qualities of tripartite interaction between plant-soil-microbe under climate change.
  11. New pyrrolopyridine-based thiazolotriazoles as diabetics inhibitors: enzymatic kinetics and in silico study
    Taha M, Rahim F, Hayat S, Chigurupati S, Khan KM, Imran S, et al.
    Future Med Chem, 2023 Mar;15(5):405-419.
    PMID: 37013918 DOI: 10.4155/fmc-2022-0306
    Aim: To synthesize pyrrolopyridine-based thiazolotriazoles as a novel class of α-amylase and α-glucosidase inhibitors and to determine their enzymatic kinetics. Methodology: Pyrrolopyridine-based thiazolotriazole analogs (1-24) were synthesized and characterized through proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance and high-resolution electron ionization mass spectrometry. Results: All synthesized analogs displayed good inhibitory potential of α-amylase and α-glucosidase ranging 17.65-70.7 μM and 18.15-71.97 μM, respectively, compared with the reference drug, acarbose (11.98 μM and 12.79 μM). Analog 3 was the most potent among the synthesized analogs, having α-amylase and α-glucosidase inhibitory activity at 17.65 and 18.15 μM, respectively. The structure-activity relationship and binding modes of interactions between selected analogs were confirmed via docking and enzymatic kinetics studies. The compounds (1-24) were tested for cytotoxicity against the 3T3 mouse fibroblast cell line and were observed to be nontoxic.
  12. Rice husk coated with copper oxide nanoparticles for 17α-ethinylestradiol removal from an aqueous solution: adsorption mechanisms and kinetics
    Alhares HS, Ali QA, Shaban MAA, M-Ridha MJ, Bohan HR, Mohammed SJ, et al.
    Environ Monit Assess, 2023 Aug 24;195(9):1078.
    PMID: 37615739 DOI: 10.1007/s10661-023-11689-6
    The 17 α-ethinylestradiol (EE2) adsorption from aqueous solution was examined using a novel adsorbent made from rice husk powder coated with CuO nanoparticles (CRH). Advanced analyses of FTIR, XRD, SEM, and EDSwere used to identify the classification parameters of a CRH-like surface morphology, configuration, and functional groups. The rice husk was coated with CuO nanoparticles, allowing it to create large surface area materials with significantly improved textural qualities with regard to functional use and adsorption performance, according to a detailed characterization of the synthesized materials. The adsorption process was applied successfully with elimination effectiveness of 100% which can be kept up to 61.3%. The parameters of adsorption were affecting the adsorption process significantly. Thermodynamic data stated that the process of adsorption was endothermic, spontaneous, chemisorption and the molecules of EE2 show affinity with the CRH. It was discovered that the adsorption process controlled by a pseudo-second-order kinetic model demonstrates that the chemisorption process was controlling EE2 removal. The Sips model is regarded as optimal for representing this practice, exhibiting a significantly high determination coefficient of 0.948. This coefficient implies that the adsorption mechanism indicates the occurrence of both heterogeneous and homogeneous adsorption. According to the findings, biomass can serve as a cheap, operative sorbent to remove estrogen from liquified solutions.
  13. Fulltext Synthesis and Molecular Docking Studies of Novel Biheterocyclic Propanamides as Antidiabetic Agents Having Mild Cytotoxicity
    Abbasi MA, Rubab K, Aziz-Ur-Rehman, Siddiqui SZ, Hassan M, Raza H, et al.
    ACS Omega, 2023 Jun 27;8(25):22899-22911.
    PMID: 37396264 DOI: 10.1021/acsomega.3c01882
    The aim of this work was to bring forth some new hybrid molecules having pharmacologically potent indole and 1,3,4-oxadiazole heterocyclic moieties unified with a propanamide entity. The synthetic methodology was initiated by esterification of 2-(1H-indol-3-yl)acetic acid (1) in a catalytic amount of sulfuric acid and ethanol in excess, to form ethyl 2-(1H-indol-3-yl)acetate (2), which was converted to 2-(1H-indol-3-yl)acetohydrazide (3) and further transformed to 5-(1H-indole-3-yl-methyl)-1,3,4-oxadiazole-2-thiol (4). 3-Bromopropanoyl chloride (5) was reacted with various amines (6a-s) in aqueous alkaline medium to generate a series of electrophiles, 3-bromo-N-(substituted)propanamides (7a-s), and these were further reacted with nucleophile 4 in DMF and NaH base to yield the targeted N-(substituted)-3-{(5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl)sulfanyl}propanamides (8a-s). The chemical structures of these biheterocyclic propanamides were confirmed by IR, 1H NMR, 13C NMR, and EI-MS spectral techniques. These compounds were evaluated for their enzyme inhibitory potentials against the α-glucosidase enzyme, where the compound 8l showed promising enzyme inhibitory potential with an IC50 value less than that of the standard acarbose. Molecular docking results of these molecules were coherent with the results of their enzyme inhibitory potentials. Cytotoxicity was assessed by the percentage of hemolytic activity method, and these compounds generally exhibited very low values as compared to the reference standard, Triton-X. Hence, some of these biheterocyclic propanamides might be considered as salient therapeutic agents in further stages of antidiabetic drug development.
  14. Fulltext Convergent synthesis, kinetics insight and allosteric computational ascriptions of thiazole-(5-aryl)oxadiazole hybrids embraced with propanamides as alkaline phosphatase inhibitors
    Butt ARS, Abbasi MA, Aziz-Ur-Rehman, Siddiqui SZ, Muhammad S, Raza H, et al.
    RSC Adv, 2023 May 02;13(20):13798-13808.
    PMID: 37197574 DOI: 10.1039/d3ra01348k
    Considering the varied pharmacological prominence of thiazole and oxadiazole heterocyclic moieties, a unique series of bi-heterocyclic hybrids, 8a-h, was synthesized in a convergent manner. The structures of newly synthesized compounds were characterized by 1H-NMR, 13C-NMR, and IR spectral studies. The structure-activity relationship of these compounds was predicted by examining their inhibitory effects against alkaline phosphatase, whereby all these molecules exhibited superb inhibitory potentials relative to the standard used. The kinetics mechanism was determined by Lineweaver-Burk plots which revealed that 8g inhibited the studied enzyme non-competitively by forming an enzyme-inhibitor complex. The inhibition constant Ki calculated from Dixon plots for this compound was 0.42 μM. The allosteric computational study was coherent with the experimental records and these ligands exhibited good binding energy values (kcal mol-1). The hemolytic analysis revealed their mild cytotoxicity towards red blood cell membranes and hence, these molecules have potential to be nontoxic medicinal scaffolds for the treatment of alkaline phosphate-associated ailments.
  15. Fulltext Synergistic Antibacterial Screening of Cymbopogon citratus and Azadirachta indica: Phytochemical Profiling and Antioxidant and Hemolytic Activities
    Hussain S, Javed W, Tajammal A, Khalid M, Rasool N, Riaz M, et al.
    ACS Omega, 2023 May 16;8(19):16600-16611.
    PMID: 37214690 DOI: 10.1021/acsomega.2c06785
    Current studies were performed to investigate the phytochemistry, synergistic antibacterial, antioxidant, and hemolytic activities of ethanolic and aqueous extracts of Azadirachta indica (EA and WA) and Cymbopogon citratus (EC and WC) leaves. Fourier transform infrared data verified the existence of alcoholic, carboxylic, aldehydic, phenyl, and bromo moieties in plant leaves. The ethanolic extracts (EA and EC) were significantly richer in phenolics and flavonoids as compared to the aqueous extracts (WA and WC). The ethanolic extract of C. citratus (EC) contained higher concentrations of caffeic acid (1.432 mg/g), synapic acid (6.743 mg/g), and benzoic acid (7.431 mg/g) as compared to all other extracts, whereas chlorogenic acid (0.311 mg/g) was present only in the aqueous extract of A. indica (WA). Food preservative properties of C. citratus can be due to the presence of benzoic acid (7.431 mg/g). -Gas chromatography-mass spectrometry analysis demonstrated the presence of 36 and 23 compounds in A. indica and C. citratus leaves, respectively. Inductively coupled plasma analysis was used to determine the concentration of 26 metals (Al, As, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Mo, Na, Ni, Pb, Sb, Se, Si, Sn, Sr, V, Zn, Zr, Ti); the metal concentrations were higher in aqueous extracts as compared to the ethanolic extracts. The extracts were generally richer in calcium (3000-7858 ppm), potassium (13662-53,750 ppm), and sodium (3181-8445 ppm) and hence can be used in food supplements as a source of these metals. Antioxidant potential (DDPH method) of C. citratus ethanolic extract was the highest (74.50 ± 0.66%), whereas it was the lowest (32.22 ± 0.28%) for the aqueous extract of A. indica. Synergistic inhibition of bacteria (Staphylococcus aureus and Escherichia coli) was observed when the aqueous extracts of both the plants were mixed together in certain ratios (v/v). The highest antibacterial potential was exhibited by the pure extract of C. citratus, which was even higher than that of the standard drug (ciprofloxacin). The plant extracts and their mixtures were more active against S. aureus as compared to E. coli. No toxic hemolytic effects were observed for the investigated extracts indicating their safe medicinal uses for human beings.
  16. Fulltext Synthesis of 1-(4-Bromobenzoyl)-1,3-dicyclohexylurea and Its Arylation via Readily Available Palladium Catalyst-Their Electronic, Spectroscopic, and Nonlinear Optical Studies via a Computational Approach
    Maqbool T, Younas H, Bilal M, Rasool N, Bajaber MA, Mubarik A, et al.
    ACS Omega, 2023 Aug 22;8(33):30306-30314.
    PMID: 37636953 DOI: 10.1021/acsomega.3c03183
    In this study, we reported the synthesis of 1-(4-bromobenzoyl)-1,3-dicyclohexylurea by the reaction of DCC (N,N'-dicyclohexylcarbodiimide) with 4-bromobenzoic acid. Subsequently, we further synthesized a new series of 1-(4-arylbenzoyl)-1,3-dicyclohexylurea (5a-g) derivatives using a Suzuki cross-coupling reaction between 1-(4-bromobenzoyl)-1,3-dicyclohexylurea (3) and various aryl/heteroaryl boronic acids (4). Thus, density functional theory (DFT) calculations have been performed to examine the electronic structure of the synthesized compounds (3, 5a-g) and to calculate their spectroscopic data. Moreover, optimized geometries and thermodynamic properties, such as frontier molecular orbitals (HOMO, LUMO), molecular electrostatic potential surfaces, and reactivity descriptors, were also calculated at the PBE0-D3BJ/def2-TZVP/SMD1,4-dioxane level of theory to validate the structures of the synthesized compounds.
  17. Synthesis and Computational Exploration of Morpholine Bearing Halogenated Sulfonamides as Potential Tyrosinase Inhibitors
    Abbasi MA, Raza H, Aziz-Ur-Rehman, Siddiqui SZ, Muhammad S, Khan FM, et al.
    Chem Biodivers, 2023 Sep;20(9):e202300257.
    PMID: 37578300 DOI: 10.1002/cbdv.202300257
    In the presented work, a new series of three different 4-((3,5-dichloro-2-[(2/4-halobenzyl)oxy]phenyl)sulfonyl)morpholines was synthesized and the structure of these compounds were corroborated by 1 H-NMR & 13 C-NMR studies. The in vitro results established all the three compounds as potent tyrosinase inhibitors relative to the standard. The Kinetics mechanism plots established that compound 8 inhibited the enzyme non-competitively. The inhibition constants Ki calculated from Dixon plots for this compound was 0.0025 μM. Additionally, computational techniques were used to explore electronic structures of synthesized compounds. Fully optimized geometries were further docked with tyrosinase enzyme for inhibition studies. Reasonably good binding/interaction energies and intermolecular interactions were obtained. Finally, drug likeness was also predicted using the rule of five (RO5) and Chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics. It is anticipated that current experimental and computational investigations will evoke the scientific interest of the research community for the above-entitled compounds.
  18. Fulltext Betamethasone Dipropionate Derivatization, Biotransformation, Molecular Docking, and ADME Analysis as Glucocorticoid Receptor
    Rashid S, Anjum S, Ahmad A, Nadeem R, Ahmed M, Shah SAA, et al.
    Biomed Res Int, 2022;2022:6865472.
    PMID: 35865666 DOI: 10.1155/2022/6865472
    Betamethasone is an important glucocorticoids (GCs), frequently used to cure allergies (such as asthma and angioedema), Crohn's disease, skin diseases (such as dermatitis and psoriasis), systemic lupus erythematosus, rheumatic disorders, and leukemia. Present investigation deals to find potential agonist of glucocorticoid receptors after biotransformation of betamethasone dipropionate (1) and to carry out the molecular docking and ADME analyses. Biotransformation of 1 was carried out with Launaea capitata (dandy) roots and Musa acuminate (banana) leaves. M. acuminate furnished low-cost value-added products such as Sananone dipropionate (2) in 5% yields. Further, biocatalysis of Sananone dipropionate (2) with M. acuminate gave Sananone propionate (3) and Sananone (4) in 12% and 7% yields, respectively. However, Sananone (4) was obtained in 37% yields from Launaea capitata. Compound 5 was obtained in 11% yield after β-elimination of propionic acid at C-17 during oxidation of compound 1. The structure elucidation of new compounds 2-5 was accomplished through combined use of X-ray diffraction and NMR (1D and 2D) studies. In addition to this, molecular docking and ADME analyses of all transformed products of 1 were also done. Compounds 1-5 showed -12.53 to -10.11 kcal/mol potential binding affinity with glucocorticoid receptor (GR) and good ADME profile. Moreover, all the compounds showed good oral bioavailability with the octanol/water partition coefficient in the range of 2.23 to 3.65, which indicated that compounds 1-5 were in significant agreement with the given criteria to be considered as drug-like.
  19. Fulltext Novel Bi-heterocycles as Potent Inhibitors of Urease and Less Cytotoxic Agents: 3-({5-((2-Amino-1,3-thiazol-4-yl)methyl)-1,3,4-oxadiazol-2-yl}sulfanyl)-N-(un/substituted-phenyl)propanamides
    Abbasi MA, Ramzan MS, Ur-Rehman A, Siddiqui SZ, Hassan M, Ali Shah SA, et al.
    Iran J Pharm Res, 2020;19(1):487-506.
    PMID: 32922502 DOI: 10.22037/ijpr.2019.13084.11362
    The synthesis of a novel series of bi-heterocyclic propanamides, 7a-l, was accomplished by S-substitution of 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol (3). The synthesis was initiated from ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate (1) which was converted to corresponding hydrazide, 2, by hydrazine hydrate in methanol. The refluxing of hydrazide, 2, with carbon disulfide in basic medium, resulted in 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol (3). A series of electrophiles, 6a-l, was synthesized by stirring un/substituted anilines (4a-l) with 3-bromopropanoyl chloride (5) in a basic aqueous medium. Finally, the targeted compounds, 7a-l, were acquired by stirring 3 with newly synthesized electrophiles, 6a-l, in DMF using LiH as a base and an activator. The structures of these bi-heterocyclic propanamides were confirmed through spectroscopic techniques, such as IR, 1H-NMR, 13C-NMR, and EI-MS. These molecules were tested for their urease inhibitory potential, whereby, the whole series exhibited very promising activity against this enzyme. Their cytotoxic behavior was ascertained through hemolysis and it was observed that all these were less cytotoxic agents. The in-silico molecular docking analysis of these molecules was also in full agreement with their in-vitro enzyme inhibition data.
  20. Fulltext Synthesis, Kinetics, Binding Conformations and Structure-activity Relationship of Potent Tyrosinase Inhibitors: Aralkylated 2-aminothiazole-ethyltriazole Hybrids
    Sadiq Butt AR, Abbasi MA, Rehman AU, Siddiqui SZ, Raza H, Hassan M, et al.
    Iran J Pharm Res, 2021;20(2):206-228.
    PMID: 34567157 DOI: 10.22037/ijpr.2020.15521.13145
    Considering the diversified pharmacological importance of thiazole and triazole heterocyclic moieties, a unique series of S-aralkylated bi-heterocyclic hybrids, 7a-l, was synthesized in a convergent manner. The structures of newly synthesized compounds were characterized by 1H-NMR, 13C-NMR, IR, and EI-MS spectral studies. The structure-activity relationship of these compounds was envisaged by analyzing their inhibitory effects against tyrosinase, whereby all these molecules exhibited potent inhibitory potentials relative to the standard used. The Kinetics mechanism was ascertained by Lineweaver-Burk plots, which revealed that 7g inhibited tyrosinase non-competitively by forming an enzyme-inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 0.0057µM. These bi-heterocyclic molecules also disclosed good binding energy values (kcal /mol) when assessed computationally. So, these molecules can be considered promising medicinal scaffolds for the treatment of skin disorders.
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