Displaying publications 21 - 40 of 42 in total

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  1. Synthesis of azachalcones, their α-amylase, α-glucosidase inhibitory activities, kinetics, and molecular docking studies
    Saleem F, Kanwal, Khan KM, Chigurupati S, Solangi M, Nemala AR, et al.
    Bioorg Chem, 2021 01;106:104489.
    PMID: 33272713 DOI: 10.1016/j.bioorg.2020.104489
    Diabetes being a chronic metabolic disorder have attracted the attention of medicinal chemists and biologists. The introduction of new and potential drug candidates for the cure and treatment of diabetes has become a major concern due to its increased prevelance worldwide. In the current study, twenty-seven azachalcone derivatives 3-29 were synthesized and evaluated for their antihyperglycemic activities by inhibiting α-amylase and α-glucosidase enzymes. Five compounds 3 (IC50 = 23.08 ± 0.03 µM), (IC50 = 26.08 ± 0.43 µM), 5 (IC50 = 24.57 ± 0.07 µM), (IC50 = 27.57 ± 0.07 µM), 6 (IC50 = 24.94 ± 0.12 µM), (IC50 = 27.13 ± 0.08 µM), 16 (IC50 = 27.57 ± 0.07 µM), (IC50 = 29.13 ± 0.18 µM), and 28 (IC50 = 26.94 ± 0.12 µM) (IC50 = 27.99 ± 0.09 µM) demonstrated good inhibitory activities against α-amylase and α-glucosidase enzymes, respectively. Acarbose was used as the standard in this study. Structure-activity relationship was established by considering the parent skeleton and different substitutions on aryl ring. The compounds were also subjected for kinetic studies to study their mechanism of action and they showed competitive mode of inhibition against both enzymes. The molecular docking studies have supported the results and showed that these compounds have been involved in various binding interactions within the active site of enzyme.
  2. 2'-Aryl and 4'-arylidene substituted pyrazolones: As potential α-amylase inhibitors
    Yousuf S, Khan KM, Salar U, Chigurupati S, Muhammad MT, Wadood A, et al.
    Eur J Med Chem, 2018 Nov 05;159:47-58.
    PMID: 30268823 DOI: 10.1016/j.ejmech.2018.09.052
    Acarbose and voglibose are well-known α-amylase inhibitors used for the management of type-II diabetes mellitus. Unfortunately, these well-known and clinically used inhibitors are also associated with several adverse effects. Therefore, there is still need to develop the safer therapy. Despite of a broad spectrum of biological significances of pyrazolone, it is infrequently evaluated for α-amylase inhibition. Current study deals with the synthesis and biological screening of aryl and arylidene substituted pyrazolones 1-18 for their potential α-amylase inhibitory activity. Structures of synthetic derivatives 1-18 were identified by different spectroscopic techniques. All compounds 1-18 (IC50 = 1.61 ± 0.16 μM to 2.38 ± 0.09 μM) exhibited significant to moderate inhibitory potential when compared to standard acarbose (IC50 = 1.46 ± 0.26 μM). A number of derivatives including 8-12 (IC50 = 1.68 ± 0.1 μM to 1.97 ± 0.07 μM) and 14-16 (IC50 = 1.61 ± 0.16 μM to 1.93 ± 0.07 μM) were found to be significantly active. Limited SAR suggested that different substitutions on compounds do not have any significant effect on the inhibitory potential. Compounds were found to be mixed-type inhibitors revealed by kinetic studies. However, in silico study was identified a number of key features participating in the interaction with the binding site of α-amylase enzyme.
  3. Flurbiprofen derivatives as novel α-amylase inhibitors: Biology-oriented drug synthesis (BIODS), in vitro, and in silico evaluation
    Khan M, Alam A, Khan KM, Salar U, Chigurupati S, Wadood A, et al.
    Bioorg Chem, 2018 12;81:157-167.
    PMID: 30125730 DOI: 10.1016/j.bioorg.2018.07.038
    Novel derivatives of flurbiprofen 1-18 including flurbiprofen hydrazide 1, substituted aroyl hydrazides 2-9, 2-mercapto oxadiazole derivative 10, phenacyl substituted 2-mercapto oxadiazole derivatives 11-15, and benzyl substituted 2-mercapto oxadiazole derivatives 16-18 were synthesized and characterized by EI-MS, 1H and 13C NMR spectroscopic techniques. All derivatives 1-18 were screened for α-amylase inhibitory activity and demonstrated a varying degree of potential ranging from IC50 = 1.04 ± 0.3 to 2.41 ± 0.09 µM as compared to the standard acarbose (IC50 = 0.9 ± 0.04 µM). Out of eighteen compounds, derivatives 2 (IC50 = 1.69 ± 0.1 µM), 3 (IC50 = 1.04 ± 0.3 µM), 9 (IC50 = 1.25 ± 1.05 µM), and 13 (IC50 = 1.6 ± 0.18 µM) found to be excellent inhibitors while rest of the compounds demonstrated comparable inhibition potential. A limited structure-activity relationship (SAR) was established by looking at the varying structural features of the library. In addition to that, in silico study was conducted to understand the binding interactions of the compounds (ligands) with the active site of α-amylase enzyme.
  4. Synthesis and study of the α-amylase inhibitory potential of thiadiazole quinoline derivatives
    Taha M, Tariq Javid M, Imran S, Selvaraj M, Chigurupati S, Ullah H, et al.
    Bioorg Chem, 2017 10;74:179-186.
    PMID: 28826047 DOI: 10.1016/j.bioorg.2017.08.003
    α-Amylase is a target for type-2 diabetes mellitus treatment. However, small molecule inhibitors of α-amylase are currently scarce. In the course of developing small molecule α-amylase inhibitors, we designed and synthesized thiadiazole quinoline analogs (1-30), characterized by different spectroscopic techniques such as 1HNMR and EI-MS and screened for α-amylase inhibitory potential. Thirteen analogs 1, 2, 3, 4, 5, 6, 22, 23, 25, 26, 27, 28 and 30 showed outstanding α-amylase inhibitory potential with IC50 values ranges between 0.002±0.60 and 42.31±0.17μM which is many folds better than standard acarbose having IC50 value 53.02±0.12μM. Eleven analogs 7, 9, 10, 11, 12, 14, 15, 17, 18, 19 and 24 showed good to moderate inhibitory potential while seven analogs 8, 13, 16, 20, 21 and 29 were found inactive. Our study identifies novel series of potent α-amylase inhibitors for further investigation. Structure activity relationship has been established.
  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. 2-Aryl benzimidazoles: Synthesis, In vitro α-amylase inhibitory activity, and molecular docking study
    Adegboye AA, Khan KM, Salar U, Aboaba SA, Kanwal, Chigurupati S, et al.
    Eur J Med Chem, 2018 Apr 25;150:248-260.
    PMID: 29533872 DOI: 10.1016/j.ejmech.2018.03.011
    Despite of many diverse biological activities exhibited by benzimidazole scaffold, it is rarely explored for the α-amylase inhibitory activity. For that purpose, 2-aryl benzimidazole derivatives 1-45 were synthesized and screened for in vitro α-amylase inhibitory activity. Structures of all synthetic compounds were deduced by various spectroscopic techniques. All compounds revealed inhibition potential with IC50 values of 1.48 ± 0.38-2.99 ± 0.14 μM, when compared to the standard acarbose (IC50 = 1.46 ± 0.26 μM). Limited SAR suggested that the variation in the inhibitory activities of the compounds are the result of different substitutions on aryl ring. In order to rationalize the binding interactions of most active compounds with the active site of α-amylase enzyme, in silico study was conducted.
  7. Synthesis, α-amylase and α-glucosidase inhibition and molecular docking studies of indazole derivatives
    Nawaz M, Taha M, Qureshi F, Ullah N, Selvaraj M, Shahzad S, et al.
    J Biomol Struct Dyn, 2022;40(21):10730-10740.
    PMID: 34463216 DOI: 10.1080/07391102.2021.1947892
    Herein, we report the synthesis and inhibitory potential of indazole (Methyl 1H-indazole-4-carboxylate) derivatives (1-13) against α-amylase and α-glucosidase enzymes. The described derivatives demonstrated good inhibitory potential with IC50 values, ranging between 15.04 ± 0.05 to 76.70 ± 0.06 µM ± SEM for α-amylase and 16.99 ± 0.19 to 77.97 ± 0.19 µM ± SEM for α-glucosidase, respectively. In particular, compounds (8-10 and 12) displayed significant inhibitory activities against both the screened enzymes, with their inhibitory potential comparable to the standard acarbose (12.98 ± 0.03 and 12.79 ± 0.17 µM ± SEM, respectively). Additionally, the influence of different substituents on enzyme inhibition activities was assessed to study the structure activity relationships. Molecular docking simulations were performed to rationalize the binding of derivatives/compounds with enzymes. All the synthesized derivatives (1-13) were characterized with the aid of spectroscopic instruments such as 1H-NMR, 13C-NMR, HR-MS, elemental analysis and FTIR.Communicated by Ramaswamy H. Sarma.
  8. 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.
  9. Fulltext Pharmacological and pharmacognostical valuation of Canna indica leaves extract by quantifying safety profile and neuroprotective potential
    Chigurupati S, Abdul Rahman Alharbi N, Sharma AK, Alhowail A, Vardharajula VR, Vijayabalan S, et al.
    Saudi J Biol Sci, 2021 Oct;28(10):5579-5584.
    PMID: 34588868 DOI: 10.1016/j.sjbs.2021.05.072
    The current study primarily focused on the pharmacognostical and phytochemical screening of Canna indica and further analyzing the leaves extract for toxicological profile and neuroprotective potential. The microscopic, dry powder properties of the leaf material and phytochemical, physicochemical analysis was evaluated for pharmacognostical assessment. Dry leaves of C. indica were extracted using methanol and then further studied for both in vitro and in vivo toxicological study. The acute toxicity was measured by estimating the antioxidant defense system and anatomical impairment in the rat's organs. Also, the neuroprotective activity of the plant extract was assessed using anticholinesterase enzymatic inhibitory assay. The extract was found to be hemocompatible and showed absences of induction of behavioural changes. Likewise, no changes were seen on the anatomical structure of the rat's organs. The methanolic extract portrayed a significant upsurge in the reduced glutathione level and showed a comparable acetylcholinesterase inhibition in a dosedependent manner with an IC50 value of 14.53 μg/mL compared to the standard Donepezil with an IC50 value of 13.31 μg/mL. C. indica has compelling pharmacognostical characteristics, good safety reports, and significant antioxidant as well as the neuroprotective potential that shows great potential for its further in-depth research for pharmacological use.
  10. Fulltext Antibacterial and Antibiofilm Activities of Nonpolar Extracts of Allium stipitatum Regel. against Multidrug Resistant Bacteria
    Karunanidhi A, Ghaznavi-Rad E, Hamat RA, Pichika MR, Lung LTT, Mohd Fauzi F, et al.
    Biomed Res Int, 2018;2018:9845075.
    PMID: 30105271 DOI: 10.1155/2018/9845075
    The present study assessed the in vitro antibacterial and antibiofilm potential of hexane (ASHE) and dichloromethane (ASDE) extracts of Allium stipitatum (Persian shallot) against planktonic cells and biofilm structures of clinically significant antibiotic resistant pathogens, with a special emphasis on methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and emerging pathogens, Acinetobacter baumannii and Stenotrophomonas maltophilia. Antibacterial activities were determined through disk diffusion, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), time-kill kinetics, and electron microscopy. Antibiofilm activity was assessed by XTT [2,3-bis(2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide] reduction assay and by confocal laser scanning microscopy (CLSM). The zone of inhibition ranged from 13 to 33 mm, while the MICs and MBCs ranged from 16 to 1024 μg mL-1. Both ASHE and ASDE completely eradicated overnight cultures of the test microorganisms, including antibiotic resistant strains. Time-kill studies showed that the extracts were strongly bactericidal against planktonic cultures of S. aureus, MRSA, Acinetobacter baumannii, and S. maltophilia as early as 4 hours postinoculation (hpi). ASHE and ASDE were shown to inhibit preformed biofilms of the four biofilm phenotypes tested. Our results demonstrate the potential therapeutic application of ASHE and ASDE to inhibit the growth of gram-positive and gram-negative biofilms of clinical significance and warrant further investigation of the potential of A. stipitatum bulbs against biofilm-related drug resistance.
  11. Fulltext In vitro antioxidant and in vivo antidepressant activity of green synthesized azomethine derivatives of cinnamaldehyde
    Chigurupati S, Shaikh SA, Mohammad JI, Selvarajan KK, Nemala AR, Khaw CH, et al.
    Indian J Pharmacol, 2017 10 17;49(3):229-235.
    PMID: 29033482 DOI: 10.4103/ijp.IJP_293_16
    OBJECTIVES: In this study, three (CS-1 to CS-3) azomethine derivatives of cinnamaldehyde were green synthesized, characterized, and their antioxidant and antidepressant activities were explored.

    MATERIALS AND METHODS: The antioxidant effect of these compounds was initially performed in vitro using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay methods before subjecting them to in vivo experiments. Compounds showing potent antioxidant activity (CS-1 and CS-2) were investigated further for their antidepressant activity using the forced swim test (FST) and tail suspension test (TST). Ascorbic acid (AA) and fluoxetine (20 mg/kg, p.o) were used as reference drugs for comparison in the antioxidant and antidepressant experiments, respectively.

    RESULTS: It was observed that CS-2 and CS-3 exhibited highest DPPH (half maximal inhibitory concentration [IC50]: 16.22 and 25.18 μg/mL) and ABTS (IC50: 17.2 and 28.86 μg/mL) radical scavenging activity, respectively, compared to AA (IC50: 15.73 and 16.79 μg/mL) and therefore, both CS-2 and CS-3 were tested for their antidepressant effect using FST and TST as experimental models. Pretreatment of CS-2 and CS-3 (20 mg/kg) for 10 days considerably decreased the immobility time in both the FST and TST models.

    CONCLUSION: The antioxidant and antidepressant effect of CS-2 and CS-3 may be attributed to the presence of azomethine linkage in the molecule.

  12. Syntheses, in vitro α-amylase and α-glucosidase dual inhibitory activities of 4-amino-1,2,4-triazole derivatives their molecular docking and kinetic studies
    Yeye EO, Kanwal, Mohammed Khan K, Chigurupati S, Wadood A, Ur Rehman A, et al.
    Bioorg Med Chem, 2020 06 01;28(11):115467.
    PMID: 32327353 DOI: 10.1016/j.bmc.2020.115467
    Thirty-three 4-amino-1,2,4-triazole derivatives 1-33 were synthesized by reacting 4-amino-1,2,4-triazole with a variety of benzaldehydes. The synthetic molecules were characterized via1H NMR and EI-MS spectroscopic techniques and evaluated for their anti-hyperglycemic potential. Compounds 1-33 exhibited good to moderate in vitro α-amylase and α-glucosidase inhibitory activities in the range of IC50 values 2.01 ± 0.03-6.44 ± 0.16 and 2.09 ± 0.08-6.54 ± 0.10 µM as compared to the standard acarbose (IC50 = 1.92 ± 0.17 µM) and (IC50 = 1.99 ± 0.07 µM), respectively. The limited structure-activity relationship suggested that different substitutions on aryl part of the synthetic compounds are responsible for variable activity. Kinetic study predicted that compounds 1-33 followed mixed and non-competitive type of inhibitions against α-amylase and α-glucosidase enzymes, respectively. In silico studies revealed that both triazole and aryl ring along with different substitutions were playing an important role in the binding interactions of inhibitors within the enzyme pocket. The synthetic molecules were found to have dual inhibitory potential against both enzymes thus they may serve as lead candidates for the drug development and research in the future studies.
  13. Synthesis of indole-based-thiadiazole derivatives as a potent inhibitor of α-glucosidase enzyme along with in silico study
    Alomari M, Taha M, Rahim F, Selvaraj M, Iqbal N, Chigurupati S, et al.
    Bioorg Chem, 2021 03;108:104638.
    PMID: 33508679 DOI: 10.1016/j.bioorg.2021.104638
    A series of nineteen (1-19) indole-based-thiadiazole derivatives were synthesized, characterized by 1HNMR, 13C NMR, MS, and screened for α-glucosidase inhibition. All analogs showed varied α-glucosidase inhibitory potential with IC50 value ranged between 0.95 ± 0.05 to 13.60 ± 0.30 µM, when compared with the standard acarbose (IC50 = 1.70 ± 0.10). Analogs 17, 2, 1, 9, 7, 3, 15, 10, 16, and 14 with IC50 values 0.95 ± 0.05, 1.10 ± 0.10, 1.30 ± 0.10, 1.60 ± 0.10, 2.30 ± 0.10, 2.30 ± 0.10, 2.80 ± 0.10, 4.10 ± 0.20 and 4.80 ± 0.20 µM respectively showed highest α-glucosidase inhibition. All other analogs also exhibit excellent inhibitory potential. Structure activity relationships have been established for all compounds primarily based on substitution pattern on the phenyl ring. Through molecular docking study, binding interactions of the most active compounds were confirmed. We further studied the kinetics study of analogs 1, 2, 9 and 17 and found that they are Non-competitive inhibitors.
  14. Synthesis of alpha amylase inhibitors based on privileged indole scaffold
    Noreen T, Taha M, Imran S, Chigurupati S, Rahim F, Selvaraj M, et al.
    Bioorg Chem, 2017 06;72:248-255.
    PMID: 28482265 DOI: 10.1016/j.bioorg.2017.04.010
    Twenty five derivatives of indole carbohydrazide (1-25) had been synthesized. These compounds were characterized using 1H NMR and EI-MS, and further evaluated for their α-amylase inhibitory potential. The analogs (1-25) showed varying degree of α-amylase inhibitory potential. ranging between 9.28 and 599.0µM when compared with standard acarbose having IC50 value 8.78±0.16µM. Six analogs, 25 (IC50=9.28±0.153µM), 22 (IC50=9.79±0.43µM), 4 (IC50=11.08±0.357µM), 1 (IC50=12.65±0.169µM), 8 (IC50=21.37±0.07µM) and 14 (IC50=43.21±0.14µM) showed potent α-amylase inhibition as compared to the standard acarbose (IC50=8.78±0.16µM). All other analogs displayed good to moderate inhibitory potential. Structure-activity relationship was established through the interaction of the active compounds with enzyme active site with the help of docking studies.
  15. Biology-oriented drug synthesis (BIODS) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl ether derivatives, in vitro α-amylase inhibitory activity and in silico studies
    Taha M, Imran S, Ismail NH, Selvaraj M, Rahim F, Chigurupati S, et al.
    Bioorg Chem, 2017 10;74:1-9.
    PMID: 28719801 DOI: 10.1016/j.bioorg.2017.07.001
    A new library of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl ether derivatives (1-23) were synthesized and characterized by EI-MS and 1H NMR, and screened for their α-amylase inhibitory activity. Out of twenty-three derivatives, two molecules 19 (IC50=0.38±0.82µM) and 23 (IC50=1.66±0.14µM), showed excellent activity whereas the remaining compounds, except 10 and 17, showed good to moderate inhibition in the range of IC50=1.77-2.98µM when compared with the standard acarbose (IC50=1.66±0.1µM). A plausible structure-activity relationship has also been presented. In addition, in silico studies was carried out in order to rationalize the binding interaction of compounds with the active site of enzyme.
  16. Synthesis of indole derivatives as diabetics II inhibitors and enzymatic kinetics study of α-glucosidase and α-amylase along with their in-silico study
    Taha M, Alrashedy AS, Almandil NB, Iqbal N, Anouar EH, Nawaz M, et al.
    Int J Biol Macromol, 2021 Nov 01;190:301-318.
    PMID: 34481854 DOI: 10.1016/j.ijbiomac.2021.08.207
    In this study, we have investigated a series of indole-based compounds for their inhibitory study against pancreatic α-amylase and intestinal α-glucosidase activity. Inhibitors of carbohydrate degrading enzymes appear to have an essential role as antidiabetic drugs. All analogous exhibited good to moderate α-amylase (IC50 = 3.80 to 47.50 μM), and α-glucosidase inhibitory interactions (IC50 = 3.10-52.20 μM) in comparison with standard acarbose (IC50 = 12.28 μM and 11.29 μM). The analogues 4, 11, 12, 15, 14 and 17 had good activity potential both for enzymes inhibitory interactions. Structure activity relationships were deliberated to propose the influence of substituents on the inhibitory potential of analogues. Docking studies revealed the interaction of more potential analogues and enzyme active site. Further, we studied their kinetic study of most active compounds showed that compounds 15, 14, 12, 17 and 11 are competitive for α-amylase and non- competitive for α-glucosidase.
  17. Fulltext Targeting natural products against SARS-CoV-2
    Al-Harrasi A, Behl T, Upadhyay T, Chigurupati S, Bhatt S, Sehgal A, et al.
    Environ Sci Pollut Res Int, 2022 Jun;29(28):42404-42432.
    PMID: 35362883 DOI: 10.1007/s11356-022-19770-2
    The human coronavirus disease (COVID-19) pandemic is caused by a novel coronavirus; the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). Natural products, secondary metabolites show positive leads with antiviral and immunotherapy treatments using genomic studies in silico docking. In addition, it includes the action of a mechanism targeting the SARS-CoV-2. In this literature, we aimed to evaluate the antiviral movement of the NT-VRL-1 unique terpene definition to Human coronavirus (HCoV-229E). The effects of 19 hydrolysable tannins on the SARS-CoV-2 were therefore theoretically reviewed and analyzed utilising the molecular operating surroundings for their C-Like protease 3CLpro catalytic dyad residues Angiotensin converting enzyme-2 (MOE 09). Pedunculagin, tercatan, and castalin were detected as interacting strongly with SARS-receptor Cov-2's binding site and catalytic dyad (Cys145 and His41). SARS-CoV-2 methods of subunit S1 (ACE2) inhibit the interaction of the receiver with the s-protein once a drug molecule is coupled to the s-protein and prevent it from infecting the target cells in alkaloids. Our review strongly demonstrates the evidence that natural compounds and their derivatives can be used against the human coronavirus and serves as an area of research for future perspective.
  18. Exploring the focal role of LRRK2 kinase in Parkinson's disease
    Kumar S, Behl T, Sehgal A, Chigurupati S, Singh S, Mani V, et al.
    Environ Sci Pollut Res Int, 2022 Feb 11.
    PMID: 35147886 DOI: 10.1007/s11356-022-19082-5
    The major breakthroughs in our knowledge of how biology plays a role in Parkinson's disease (PD) have opened up fresh avenues designed to know the pathogenesis of disease and identify possible therapeutic targets. Mitochondrial abnormal functioning is a key cellular feature in the pathogenesis of PD. An enzyme, leucine-rich repeat kinase 2 (LRRK2), involved in both the idiopathic and familial PD risk, is a therapeutic target. LRRK2 has a link to the endolysosomal activity. Enhanced activity of the LRRK2 kinase, endolysosomal abnormalities and aggregation of autophagic vesicles with imperfectly depleted substrates, such as α-synuclein, are all seen in the substantia nigra dopaminergic neurons in PD. Despite the fact that LRRK2 is involved in endolysosomal and autophagic activity, it is undefined if inhibiting LRRK2 kinase activity will prevent endolysosomal dysfunction or minimise the degeneration of dopaminergic neurons. The inhibitor's capability of LRRK2 kinase to inhibit endolysosomal and neuropathological alterations in human PD indicates that LRRK2 inhibitors could have significant therapeutic usefulness in PD. G2019S is perhaps the maximum common mutation in PD subjects. Even though LRRK2's well-defined structure has still not been established, numerous LRRK2 inhibitors have been discovered. This review summarises the role of LRRK2 kinase in Parkinson's disease.
  19. Exploring the effect of Crinum latifolia in obesity: possible role of oxidative, angiogenic, and inflammatory pathways
    Nijhawan P, Behl T, Chigurupati S, Sehgal A, Singh S, Sharma N, et al.
    Environ Sci Pollut Res Int, 2022 Jan 07.
    PMID: 34997511 DOI: 10.1007/s11356-022-18531-5
    Obesity is a multifaceted disease encompassing deposition of an unnecessary amount of fat which upsurges the possibility of other complications, viz., hypertension and certain type of cancers. Although obesity results from combination of genetic factors, improper diet and inadequate physical exercise also play a major role in its onset. The present study aims at exploring the anti-obesity activity of Crinum latifolia leaf extract in obese rats. The leaves were extracted using hydroalcoholic extraction which was later diluted with water and given to obese rats. The dosing was started from the 4th week (by oral administration of extract of Crinum latifolia (100 mg/kg and 200 mg/kg) and combination of Crinum latifolia leaf extract 200 mg/kg and orlistat 30 mg/kg) till the 10th week. Various angiogenic, antioxidant, biochemical, and inflammatory biomarkers were assessed at the end of the study. The obese symptoms were progressively reduced in treatment groups when compared to disease control groups. The angiogenic parameters and inflammatory parameters were consequently reduced in treatment groups. The oxidative parameters superoxide dismutase (SOD) and catalase were gradually increased, while levels of TBARS were reduced in treatment groups showing antioxidant nature of leaf hydroalcoholic extract. The Crinum latifolia leaf extract possesses anti-obesity properties and therefore can be used as a therapeutic option in the management of obesity.
  20. Fulltext Bioactive 2-(Methyldithio)Pyridine-3-Carbonitrile from Persian Shallot (Allium stipitatum Regel.) Exerts Broad-Spectrum Antimicrobial Activity
    Karunanidhi A, Ghaznavi-Rad E, Jeevajothi Nathan J, Joseph N, Chigurupati S, Mohd Fauzi F, et al.
    Molecules, 2019 Mar 13;24(6).
    PMID: 30871159 DOI: 10.3390/molecules24061003
    Antibiotic resistance is a problem that continues to challenge the healthcare sector, especially in clinically significant pathogens like methicillin-resistant Staphylococcus aureus (MRSA). Herein is described the isolation and structure elucidation of a bioactive compound from Allium stipitatum with antimicrobial activity. Crude Allium stipitatum dichloromethane extract (ASDE) was subjected to systematic purification by chromatographic procedures to afford various bioactive fractions. A fraction that exhibited anti-MRSA activity (4 µg·mL-1) was further characterized to determine the structure. The structure of the compound was elucidated as 2-(methyldithio)pyridine-3-carbonitrile (2-Medpy-3-CN). The 2-Medpy-3-CN compound, which was screened for antimicrobial activity, exhibited minimum inhibitory concentrations (MICs) in the range of 0.5 to >64 µg·mL-1 for tested bacterial species and 0.25 to 2 µg·mL-1 for Candida spp. Further studies are important to confirm the drug target and mechanism of action.
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