Displaying publications 161 - 180 of 343 in total

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  1. Antioxidant and anticholinesterase potential of diterpenoid alkaloids from Aconitum heterophyllum
    Ahmad H, Ahmad S, Shah SAA, Latif A, Ali M, Khan FA, et al.
    Bioorg Med Chem, 2017 07 01;25(13):3368-3376.
    PMID: 28457693 DOI: 10.1016/j.bmc.2017.04.022
    Extensive chromatographic separations performed on the basic (pH=8-10) chloroform soluble fraction of Aconitum heterophyllum resulted in the isolation of three new diterpenoid alkaloids, 6β-Methoxy, 9β-dihydroxylheteratisine (1), 1α,11,13β-trihydroxylhetisine (2), 6,15β-dihydroxylhetisine (3), and the known compounds iso-atisine (4), heteratisine (5), hetisinone (6), 19-epi-isoatisine (7), and atidine (8). Structures of the isolated compounds were established by means of mass and NMR spectroscopy as well as single crystal X-ray crystallography. Compounds 1-8 were screened for their antioxidant and enzyme inhibition activities followed by in silico studies to find out the possible inhibitory mechanism of the tested compounds. This work is the first report demonstrating significant antioxidant and anticholinesterase potentials of diterpenoid alkaloids isolated from a natural source.
  2. Synthesis, SAR elucidations and molecular docking study of newly designed isatin based oxadiazole analogs as potent inhibitors of thymidine phosphorylase
    Javid MT, Rahim F, Taha M, Nawaz M, Wadood A, Ali M, et al.
    Bioorg Chem, 2018 09;79:323-333.
    PMID: 29803079 DOI: 10.1016/j.bioorg.2018.05.011
    Thymidine phosphorylase is an enzyme involved in pyrimidine salvage pathway that is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and gliostatin. It is enormously up regulated in a variety of solid tumors. Furthermore, surpassing of TP level protects tumor cells from apoptosis and helps cell survival. Thus TP is identified as a prime target for developing novel anticancer therapies. A new class of exceptionally potent isatin based oxadiazole (1-30) has been synthesized and evaluated for thymidine phosphorylase inhibitory potential. All analogs showed potent thymidine phosphorylase inhibition when compared with standard 7-Deazaxanthine, 7DX (IC50 = 38.68 ± 1.12 µM). Molecular docking study was performed in order to determine the binding interaction of these newly synthesized compounds, which revealed that these synthesized compounds established stronger hydrogen bonding network with active site of residues as compare to the standard compound 7DX.
  3. Norditerpenoid alkaloids of Delphinium denudatum as cholinesterase inhibitors
    Ahmad H, Ahmad S, Ali M, Latif A, Shah SAA, Naz H, et al.
    Bioorg Chem, 2018 08;78:427-435.
    PMID: 29698893 DOI: 10.1016/j.bioorg.2018.04.008
    Three new norditerpenoids alkaloids, 1β-hydroxy,14β-acetyl condelphine (1), jadwarine-A (2), jadwarine-B (3) along with two known alkaloids isotalatizidine hydrate (4) and dihydropentagynine (5) were isolated from medicinal plant Delphinium denudatum. The structures of natural products 1-5 were established on the basis of HR-EIMS, 1H and 13C NMR (1D & 2D) spectroscopic data as well as by comparison from literature data. The structures of compound 1 and 4 were also confirmed by single crystal X-ray diffraction studies. In-vitro AChE and BChE enzyme inhibitory activities of compounds 1-5 and molecular docking studies were performed to investigate the possible molecular inhibitory mechanism of the isolated natural products. Compound 2, 4 and 5 showed competitive inhibitory effects by inhibiting AChE and BChE, respectively, while 1 and 3 showed non-competitive inhibition. This work is the first report that provides a supporting evidence about the use of constituents of Delphinium denudatum in cerebral dementia and Alzheimer diseases.
  4. Synthesis, α-glucosidase inhibitory activity and in silico study of tris-indole hybrid scaffold with oxadiazole ring: As potential leads for the management of type-II diabetes mellitus
    Taha M, Rahim F, Imran S, Ismail NH, Ullah H, Selvaraj M, et al.
    Bioorg Chem, 2017 10;74:30-40.
    PMID: 28750203 DOI: 10.1016/j.bioorg.2017.07.009
    Discovery of α-glucosidase inhibitors has been actively pursued with the aim to develop therapeutics for the treatment of type-II diabetes mellitus and the other carbohydrate mediated disease. In continuation of our drug discovery research on potential antidiabetic agents, we synthesized novel tris-indole-oxadiazole hybrid analogs (1-21), structurally characterized by various spectroscopic techniques such as 1H NMR, EI-MS, and 13C NMR. Elemental analysis was found in agreement with the calculated values. All compounds were evaluated for α-glucosidase inhibiting potential and showed potent inhibitory activity in the range of IC50=2.00±0.01-292.40±3.16μM as compared to standard acarbose (IC50=895.09±2.04µM). The pharmacokinetic predictions of tris-indole series using descriptor properties showed that almost all compounds in this series indicate the drug aptness. Detailed binding mode analyses with docking simulation was also carried out which showed that the inhibitors can be stabilized by the formation of hydrogen bonds with catalytic residues and the establishment of hydrophobic contacts at the opposite side of the active site.
  5. Fulltext Dataset on the effect of receiver size and acceptance half-angle on the aperture width and height of compound parabolic concentrator for low-concentrating photovoltaic applications using RSM
    Masood F, Nor NBM, Nallagownden P, Elamvazuthi I, Alam MA, Yusuf M, et al.
    Data Brief, 2021 Dec;39:107630.
    PMID: 34988268 DOI: 10.1016/j.dib.2021.107630
    The combined effect of design control factors on the response variables gives valuable information for geometric design optimization of the compound parabolic concentrator. This study presents the data related to the statistical modeling and analysis of variance for aperture width and height of a low concentration symmetric compound parabolic concentrator designed for photovoltaic applications. The design matrix was generated using the response surface modeling approach. The geometric design equations of the proposed concentrator were developed and solved analytically using MATLAB. The empirical models were developed to establish relationships between the control factors and response variables of the proposed system. The analysis of variance was conducted for two significant response variables. The developed statistical models can be used to predict the selected response variables within the permissible range. The presented data can be used for statistical modeling and design optimization of the two-dimensional symmetric compound parabolic concentrator.
  6. 3,4-Dimethoxybenzohydrazide derivatives as antiulcer: Molecular modeling and density functional studies
    Taha M, Ismail NH, Zaki HM, Wadood A, Anouar EH, Imran S, et al.
    Bioorg Chem, 2017 12;75:235-241.
    PMID: 29031169 DOI: 10.1016/j.bioorg.2017.10.004
    3,4-Dimethoxybenzohydrazide derivatives (1-25) have been synthesized and evaluated for their urease inhibitory potential. Among the series, compounds 2, 3, 4 and 5 with IC50 values 12.61 ± 0.07, 18.24 ± 0.14, 19.22 ± 0.21, and 8.40 ± 0.05 µM, respectively, showed excellent urease inhibitory potentials when compared with standard thiourea (IC50 value 21.40 ± 0.21 µM). Compounds 1, 6, 8, 18, 19 and 20 also showed good to moderate inhibition, while the remaining compounds were found to be completely inactive. The structures of compounds 6 and 25 were confirmed through X-ray crystallography while the structures of remaining compounds were confirmed through ESI-MS and 1H NMR. Molecular docking studies were performed understand the binding interactions with enzyme active site. The synthesized compounds were evaluated for cytotoxicity and found to be nontoxic.
  7. Bisindolylmethane thiosemicarbazides as potential inhibitors of urease: Synthesis and molecular modeling studies
    Taha M, Ullah H, Al Muqarrabun LMR, Khan MN, Rahim F, Ahmat N, et al.
    Bioorg Med Chem, 2018 01 01;26(1):152-160.
    PMID: 29183662 DOI: 10.1016/j.bmc.2017.11.028
    Bisindolylmethane thiosemicarbazides 1-18 were synthesized, characterized by 1H NMR and ESI MS and evaluated for urease inhibitory potential. All analogs showed outstanding urease inhibitory potentials with IC50 values ranging between 0.14 ± 0.01 to 18.50 ± 0.90 μM when compared with the standard inhibitor thiourea having IC50 value 21.25 ± 0.90 μM. Among the series, analog 9 (0.14 ± 0.01 μM) with di-chloro substitution on phenyl ring was identified as the most potent inhibitor of urease. The structure activity relationship has been also established on the basis of binding interactions of the active analogs. These binding interactions were identified by molecular docking studies.
  8. CuO improved energy band of AgO/fibrous SiO2-ZrO2 for optimized simultaneous photocatalytic redox of chromium (VI) and p-cresol using response surface methodology
    Aziz FFA, Jalil AA, Hassan NS, Fauzi AA, Khusnun NF, Ali MW, et al.
    Environ Res, 2023 Mar 01;220:115151.
    PMID: 36584845 DOI: 10.1016/j.envres.2022.115151
    Ternary CuO/AgO/FSZr photocatalysts were fabricated via the hydrothermal and electrochemical methods with three different CuO loading (1, 3 and 5 wt%), indicated as 1CuO/AgO/FSZr, 3CuO/AgO/FSZr and 5CuO/AgO/FSZr. The photocatalytic reaction was tested towards simultaneous chromium (VI) photoreduction and p-cresol photooxidation and the performance in order as follow: 3CuO/AgO/FSZr > 5CuO/AgO/FSZr > 1CuO/AgO/FSZr > AgO/FSZr > FSZr. CuO/AgO/FSZr photocatalysts showed an improvement in photocatalytic activity compared to AgO/FSZr and FSZr due to the reduction potential of chromium (VI) aligned closer to the conduction band of CuO and provided abundant free active electrons (e-) and holes (h+) with efficient transportation and migration. Interestingly, the 3CuO/AgO/FSZr was established as the best photocatalyst with 98% reduction of chromium (VI) and 83% oxidation of p-cresol simultaneously, owing to its strong corporation between the metal oxides and support and higher total pore volume. The Langmuir-Hinshelwood model were employed for kinetics which followed the pseudo-first-order kinetics model well. Based on the simultaneous photocatalytic mechanism, chromium (VI) and p-cresol were directly reduced and oxidized by e- and h+, respectively. The response surface methodology (RSM) discovered that the quadratic term initial concentration of chromium (VI) is the main significant factor in photocatalytic performance. The optimum parameters for simultaneous photoredox of chromium (VI) and p-cresol predicted from RSM are 9.6 mg L-1 of chromium (VI) concentration, 9.8 mg L-1 of p-cresol concentration and 0.32 g L-1 of catalyst dosage. Under these conditions the error between the predicted and experimental values is only 3.7%. The 3CuO/AgO/FSZr sustained the photocatalytic performance after reused for five cycles and could oxidized various organic pollutants as well as reduced chromium (VI) simultaneously.
  9. Fulltext Development of correlations between various engineering rockmass classification systems using railway tunnel data in Garhwal Himalaya, India
    Azad MA, Najeh T, Raina AK, Singh N, Ansari A, Ali M, et al.
    Sci Rep, 2024 May 10;14(1):10716.
    PMID: 38729957 DOI: 10.1038/s41598-024-60289-y
    Engineering rockmass classifications are an integral part of design, support and excavation procedures of tunnels, mines, and other underground structures. These classifications are directly linked to ground reaction and support requirements. Various classification systems are in practice and are still evolving. As different classifications serve different purposes, it is imperative to establish inter-correlatability between them. The rating systems and engineering judgements influence the assignment of ratings owing to cognition. To understand the existing correlation between different classification systems, the existing correlations were evaluated with the help of data of 34 locations along a 618-m-long railway tunnel in the Garhwal Himalaya of India and new correlations were developed between different rock classifications. The analysis indicates that certain correlations, such as RMR-Q, RMR-RMi, RMi-Q, and RSR-Q, are comparable to the previously established relationships, while others, such as RSR-RMR, RCR-Qn, and GSI-RMR, show weak correlations. These deviations in published correlations may be due to individual parameters of estimation or measurement errors. Further, incompatible classification systems exhibited low correlations. Thus, the study highlights a need to revisit existing correlations, particularly for rockmass conditions that are extremely complex, and the predictability of existing correlations exhibit high variations. In addition to augmenting the existing database, new correlations for metamorphic rocks in the Himalayan region have been developed and presented that can serve as a guide for future rock engineering projects in such formations and aid in developing appropriate excavation and rock support methodologies.
  10. Fulltext Effect of banana tree leaves ash as cementitious material on the durability of concrete against sulphate and acid attacks
    Bhutto S, Abro FU, Ali M, Buller AS, Bheel N, Gamil Y, et al.
    Heliyon, 2024 Apr 15;10(7):e29236.
    PMID: 38601592 DOI: 10.1016/j.heliyon.2024.e29236
    The construction industry's rapid growth poses challenges tied to raw material depletion and increased greenhouse gas emissions. To address this, alternative materials like agricultural residues are gaining prominence due to their potential to reduce carbon emissions and waste generation. In this context this research optimizes the use of banana leaves ash as a partial cement substitution, focusing on durability, and identifying the ideal cement-to-ash ratio for sustainable concrete. For this purpose, concrete mixes were prepared with BLA replacing cement partially in different proportions i.e. (0 %, 5 %, 10 %, 15 %, & 20 %) and were analyzed for their physical, mechanical and Durability (Acid and Sulphate resistance) properties. Compressive strength, acid resistance and sulphate resistance testing continued for 90 days with the intervals of 7, 28 and 90 days. The results revealed that up to 10 % incorporation of BLA improved compressive strength by 10 %, while higher BLA proportions (up to 20 %) displayed superior performance in durability tests as compared to the conventional mix. The results reveal the potentials of banana leave ash to refine the concrete matrix by formation of addition C-S-H gel which leads towards a better performance specially in terms of durability aspect. Hence, banana leaf ash (BLA) is an efficient concrete ingredient, particularly up to 10 % of the mix. Beyond this threshold, it's still suitable for applications where extreme strength isn't the primary concern, because there may be a slight reduction in compressive strength.
  11. Fulltext Effect of rock properties on wear and cutting performance of multi blade circular saw with iron based multi-layer diamond segments
    Rajpurohit SS, Fissha Y, Sinha RK, Ali M, Ikeda H, Ghribi W, et al.
    Sci Rep, 2024 Feb 26;14(1):4590.
    PMID: 38409139 DOI: 10.1038/s41598-024-54625-5
    This study is an attempt for comprehensive, combining experimental data with advanced analytical techniques and machine learning for a thorough understanding of the factors influencing the wear and cutting performance of multi-blade diamond disc cutters on granite blocks. A series of sawing experiments were performed to evaluate the wear and cutting performance of multi blade diamond disc cutters with varying diameters in the processing of large-sized granite blocks. The multi-layer diamond segments comprising the Iron (Fe) based metal matrix were brazed on the sawing blades. The segment's wear was studied through micrographs and data obtained from the Field Emission Scanning Electron Microscopy (FESEM) and Energy Dispersive X-ray (EDS). Granite rock samples of nine varieties were tested in the laboratory to determine the quantitative rock parameters. The contribution of individual rock parameters and their combined effects on wear and cutting performance of multi blade saw were correlated using statistical machine learning methods. Moreover, predictive models were developed to estimate the wear and cutting rate based on the most significant rock properties. The point load strength index, uniaxial compressive strength, and deformability, Cerchar abrasivity index, and Cerchar hardness index were found to be the significant variables affecting the sawing performance.
  12. Fulltext Experimental study on the eco-friendly plastic-sand paver blocks by utilising plastic waste and basalt fibers
    Iftikhar B, Alih SC, Vafaei M, Ali M, Javed MF, Asif U, et al.
    Heliyon, 2023 Jun;9(6):e17107.
    PMID: 37484238 DOI: 10.1016/j.heliyon.2023.e17107
    Plastic waste poses a significant hazard to the environment as a result of its high production rates, which endanger both the environment and its inhabitants. Similarly, another concern is the production of cement, which accounts for roughly 8% of global CO2 emissions. Thus, recycling plastic waste as a replacement for cementitious materials may be a more effective strategy for waste minimisation and cement elimination. Therefore, in this study, plastic waste (low-density polyethylene) is utilised in the production of plastic sand paver blocks without the use of cement. In addition to this, basalt fibers which is a green industrial material is also added in the production of eco-friendly plastic sand paver blocks to satisfy the standard of ASTM C902-15 of 20 N/mm2 for the light traffic. In order to make the paver blocks, the LDPE waste plastic was melted outside in the open air and then combined with sand. Variations were made to the ratio of LDPE to sand, the proportion of basalt fibers, and sand particle size. Paver blocks were evaluated for their compressive strength, water absorption, and at different temperatures. Including 0.5% percent basalt fiber of length 4 mm gives us the best result by enhancing compressive strength by 20.5% and decreasing water absorption by 50.5%. The best results were obtained with a ratio of 30:70 LDPE to sand, while the finest sand provides the greatest compressive strength. Moreover, the temperature effect was also studied from 0 to 60 °C, and the basalt fibers incorporated in plastic paver blocks showed only a 20% decrease in compressive strength at 60 °C. This research has produced eco-friendly paver blocks by removing cement and replacing it with plastic waste, which will benefit the environment, save money, reduce carbon dioxide emissions, and be suitable for low-traffic areas, all of which contribute to sustainable development.
  13. Synthesis of 2,4-dihydroxyacetophenone derivatives as potent PDE-1 and -3 inhibitors: in vitro and in silico insights
    Alam A, Gul S, Zainab, Khan M, Elhenawy AA, Islam MS, et al.
    Future Med Chem, 2024;16(12):1185-1203.
    PMID: 38989989 DOI: 10.1080/17568919.2024.2342707
    Aim: Synthesis of novel bis-Schiff bases having potent inhibitory activity against phosphodiesterase (PDE-1 and -3) enzymes, potentially offering therapeutic implications for various conditions. Methods: Bis-Schiff bases were synthesized by refluxing 2,4-dihydroxyacetophenone with hydrazine hydrate, followed by treatment of substituted aldehydes with the resulting hydrazone to obtain the product compounds. After structural confirmation, the compounds were screened for their in vitro PDE-1 and -3 inhibitory activities. Results: The prepared compounds exhibited noteworthy inhibitory efficacy against PDE-1 and -3 enzymes by comparing with suramin standard. To clarify the binding interactions between the drugs, PDE-1 and -3 active sites, molecular docking studies were carried out. Conclusion: The potent compounds discovered in this study may be good candidates for drug development.
  14. Retrospective database analysis for clinical diagnoses commonly associated with pneumococcal diseases in the Malaysian healthcare system over a 3-year period (2013-2015)
    Sundaramurthy SSR, Allen KE, Fletcher MA, Liew KF, Borhanuddin B, Ali M, et al.
    BMC Infect Dis, 2024 Jan 12;24(1):79.
    PMID: 38216882 DOI: 10.1186/s12879-023-08611-3
    BACKGROUND: Pneumococcal disease caused by Streptococcus pneumoniae is an important cause of morbidity and mortality across all ages, particularly in younger children and older adults. Here, we describe pneumococcal disease hospitalizations at Ministry of Health (MoH) facilities in Malaysia between 2013 and 2015.

    METHODS: This was a retrospective databases analysis. Tabular data from the Malaysian Health Data Warehouse (MyHDW) were used to identify microbiologically confirmed, pneumococcal disease hospitalizations and deaths during hospitalization, using hospital-assigned ICD-10 codes (i.e., classified as meningitis, pneumonia, or non-meningitis non-pneumonia). Case counts, mortality counts, and case fatality rates were reported by patient age group and by Malaysian geographic region.

    RESULTS: A total of 683 pneumococcal disease hospitalizations were identified from the analysis: 53 pneumococcal meningitis hospitalizations (5 deaths and 48 discharges), 413 pneumococcal pneumonia hospitalizations (24 deaths and 389 discharges), and 205 non-meningitis non-pneumonia pneumococcal disease hospitalizations (58 deaths and 147 discharges). Most hospitalizations occurred in children aged 

  15. Novel acyl hydrazide derivatives of polyhydroquinoline as potent anti-diabetic and anti-glycating agents: Synthesis, in vitro α-amylase, α-glucosidase inhibition and anti-glycating activity with molecular docking insights
    Ur Rahman S, Alam A, Parveen Z, Zainab, Assad M, Adnan Ali Shah S, et al.
    Bioorg Chem, 2024 Sep;150:107501.
    PMID: 38865858 DOI: 10.1016/j.bioorg.2024.107501
    In this study, eleven novel acyl hydrazides derivative of polyhydroquinoline were synthesized, characterized and screened for their in vitro anti-diabetic and anti-glycating activities. Seven compounds 2a, 2d, 2i, 2 h, 2j, 2f, and 2 g exhibited notable α-amylase inhibitory activity having IC50 values from 3.51 ± 2.13 to 11.92 ± 2.30 µM. Similarly, six compounds 2d, 2f, 2 h, 2i, 2j, and 2 g displayed potent α-glucosidase inhibitory activity compared to the standard acarbose. Moreover, eight derivatives 2d, 2 g, 2f, 2j, 2a, 2i, 2 g, and 2e showed excellent anti-glycating activity with IC50 values from 6.91 ± 2.66 to 15.80 ± 1.87 µM when compared them with the standard rutin (IC50 = 22.5 ± 0.90 µM). Molecular docking was carried out to predict the binding modes of all the compounds with α-amylase and α-glucosidase. The docking analysis revealed that most of the compounds established strong interactions with α-amylase and α-glucosidase. All compounds fitted well into the binding pockets of α-amylase and α-glucosidase. Among all compounds 2a and 2f were most potent based on docking score -8.2515 and -7.3949 against α-amylase and α-glucosidase respectively. These results hold promise for the development of novel candidates targeted at controlling postprandial glucose levels in individuals with diabetes.
  16. Benzothiazole Derived Ether Hybrids as Potent Anti-Thymidine Phosphorylase Agents: Synthesis, In Vitro, and Computational Investigations
    Usman M, Alam A, Zainab, Khan M, Tüzün B, Ayaz M, et al.
    Chem Biodivers, 2025 Feb 13.
    PMID: 39946148 DOI: 10.1002/cbdv.202403385
    This work is based on the synthesis of new ether derivatives bearing benzothiazole (BTA) scaffold through multistep reaction process. Initially, BTA was prepared by refluxing 4-hydroxybenzaldehyde with aminothiophenol having sodium metabisulfite in dimethylformamide (DMF); subsequently, the product was further refluxed with different substituted benzyl and alkyl bromides in acetone to get ether hybrids of BTA in good yields. Structurally, these compounds were confirmed by means of 1H, 13C-NMR, and mass spectrometry and evaluated for in vitro thymidine phosphorylase (TP) inhibitory activity. In the series, seven compounds attributed excellent inhibition against TP enzyme better than the standard. Similarly, three compounds showed good activity, whereas two compounds were found inactive. Moreover, all these compounds showed no toxicity to normal human fibroblast cell line (BJ cell line). In addition, Gaussian calculations were performed on the 6-31++g(d,p) basis set to examine the 13 synthesized compounds at the B3LYP, HF, and M062X levels. Additionally, molecular docking calculations were performed on TP enzyme proteins (PDB IDs: 4EAD, 2WK6, and 4LHM), and absorption, distribution, metabolism, excretion/toxicity (ADME/T) calculations were performed to investigate the effects and responses of these compounds in human metabolism.
  17. Synthesis of novel derivatives of 4-methylbenzimidazole and evaluation of their biological activities
    Taha M, Ismail NH, Jamil W, Rashwan H, Kashif SM, Sain AA, et al.
    Eur J Med Chem, 2014 Sep 12;84:731-8.
    PMID: 25069019 DOI: 10.1016/j.ejmech.2014.07.078
    4-Methylbenzimidazole 1-28 novel derivatives were synthesized and evaluated for their antiglycation and antioxidant activities. Compounds 1-7 and 11 showed excellent activities ranged 140-280 μM, better than standard drug rutin (294.46 ± 1.50 μM). Compound 1-28 were also evaluated for DPPH activities. Compounds 1-8 showed excellent activities, ranging 12-29 μM, better than standard drug n-propylgallate (IC50 = 30.30 ± 0.40 μM). For superoxide anion scavenging activity, compounds 1-7 showed better activity than standard n-propylgallate (IC50 = 106.34 ± 1.6 μM), ranged 82-104 μM. These compounds were found to be nontoxic to THP-1 cells.
  18. Evaluation of 2-indolcarbohydrazones as potent α-glucosidase inhibitors, in silico studies and DFT based stereochemical predictions
    Taha M, Ismail NH, Javaid K, Imran S, Anouar el H, Wadood A, et al.
    Bioorg Chem, 2015 Dec;63:24-35.
    PMID: 26398141 DOI: 10.1016/j.bioorg.2015.09.001
    2-Indolcarbohydrazones 1-28 were synthesized and evaluated for their α-glucosidase inhibitory potential. A varying degree of inhibitory potential with IC50 values in the range of 2.3±0.11-226.4±6.8μM was observed while comparing these outcomes with the standard acarbose (IC50=906.0±6.3μM). The stereochemistry of ten (10) randomly selected compounds (1, 3, 6, 8, 12, 18, 19, 23, 25 and 28) was predicted by Density Functional Theory (DFT). The stability of E isomer was deduced by comparing the calculated and experimental vibration modes of νCO, νNC and νCH (CH in NCH-R). It was observed that except compound 18, all other compounds were deduced to have E configuration while molecular modeling studies revealed the key interactions between enzyme and synthesized compounds.
  19. Synthesis of symmetrical bis-Schiff base-disulfide hybrids as highly effective anti-leishmanial agents
    Taha M, Sain AA, Ali M, Anouar EH, Rahim F, Ismail NH, et al.
    Bioorg Chem, 2020 06;99:103819.
    PMID: 32325334 DOI: 10.1016/j.bioorg.2020.103819
    Leishmaniasis has affected a wider part of population around the globe. Most often, the existing regiments to battle against leishmaniasis are inadequate and limited. In our ongoing efforts to develop new leishmanicidal agents, we have synthesized a series of novel and symmetrical bis-Schiff base-disulfide hybrids 1-27. Intermediate disulfide was synthesized from corresponding 2-aminothiol followed by reacting the coupled adduct with various aromatic aldehydes. All these compounds showed outstanding inhibition when compared with standard (Table 1). Out of twenty seven analogues, twenty two analogues i.e. 1-5, 7-13, 17-21, 23-27 analogues showed excellent inhibitory potential with EC50 values ranging from 0.010 ± 0.00 to 0.096 ± 0.01 μM while five compounds i.e. 6, 14-16, and 22 showed good inhibitory potential with EC50 values ranging from 0.10 ± 0.00 to 0.137 ± 0.01 μM when compared with the standard Amphotericin B. Structure-activity relationship has been established while molecular docking studies were performed to pin the binding interaction of active molecules. This study will help to develop new antileishmanial lead compounds.
  20. Fulltext Synthesis of Chromen-4-One-Oxadiazole Substituted Analogs as Potent β-Glucuronidase Inhibitors
    Taha M, Rahim F, Ali M, Khan MN, Alqahtani MA, Bamarouf YA, et al.
    Molecules, 2019 Apr 18;24(8).
    PMID: 31003424 DOI: 10.3390/molecules24081528
    Chromen-4-one substituted oxadiazole analogs 1-19 have been synthesized, characterized and evaluated for β-glucuronidase inhibition. All analogs exhibited a variable degree of β-glucuronidase inhibitory activity with IC50 values ranging in between 0.8 ± 0.1-42.3 ± 0.8 μM when compared with the standard d-saccharic acid 1,4 lactone (IC50 = 48.1 ± 1.2 μM). Structure activity relationship has been established for all compounds. Molecular docking studies were performed to predict the binding interaction of the compounds with the active site of enzyme.
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