Displaying publications 1 - 20 of 42 in total

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  1. BIN1 in the Pursuit of Ousting the Alzheimer's Reign: Impact on Amyloid and Tau Neuropathology
    Kaur I, Behl T, Sundararajan G, Panneerselvam P, Vijayakumar AR, Senthilkumar GP, et al.
    Neurotox Res, 2023 Oct 17.
    PMID: 37847429 DOI: 10.1007/s12640-023-00670-3
    Alzheimer's disease contributes to 60-70% of all dementia cases in the general population. Belonging to the BIN1/amphiphysin/RVS167 (BAR) superfamily, the bridging integrator (BIN1) has been identified to impact two major pathological hallmarks in Alzheimer's disease (AD), i.e., amyloid beta (Aβ) and tau accumulation. Aβ accumulation is found to increase by BIN1 knockdown in cortical neurons in late-onset AD, due to BACE1 accumulation at enlarged early endosomes. Two BIN1 mutants, KR and PL, were identified to exhibit Aβ accumulation. Furthermore, BIN1 deficiency by BIN1-related polymorphisms impairs the interaction with tau, thus elevating tau phosphorylation, altering synapse structure and tau function. Even though the precise role of BIN1 in the neuronal tissue needs further investigation, the authors aim to throw light on the potential of BIN1 and unfold its implications on tau and Aβ pathology, to aid AD researchers across the globe to examine BIN1, as an appropriate target gene for disease management.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. Fulltext Targeting Probiotics in Rheumatoid Arthritis
    Bungau SG, Behl T, Singh A, Sehgal A, Singh S, Chigurupati S, et al.
    Nutrients, 2021 Sep 26;13(10).
    PMID: 34684377 DOI: 10.3390/nu13103376
    Rheumatoid arthritis (RA) is a progressive inflammatory disorder characterized by swollen joints, discomfort, tightness, bone degeneration and frailty. Genetic, agamogenetic and sex-specific variables, Prevotella, diet, oral health and gut microbiota imbalance are all likely causes of the onset or development of RA, perhaps the specific pathways remain unknown. Lactobacillus spp. probiotics are often utilized as relief or dietary supplements to treat bowel diseases, build a strong immune system and sustain the immune system. At present, the action mechanism of Lactobacillus spp. towards RA remains unknown. Therefore, researchers conclude the latest analysis to effectively comprehend the ultimate pathogenicity of rheumatoid arthritis, as well as the functions of probiotics, specifically Lactobacillus casei or Lactobacillus acidophilus, in the treatment of RA in therapeutic and diagnostic reports. RA is a chronic inflammation immunological illness wherein the gut microbiota is affected. Probiotics are organisms that can regulate gut microbiota, which may assist to relieve RA manifestations. Over the last two decades, there has been a surge in the use of probiotics. However, just a few research have considered the effect of probiotic administration on the treatment and prevention of arthritis. Randomized regulated experimental trials have shown that particular probiotics supplement has anti-inflammatory benefits, helps people with RA enhance daily activities and alleviates symptoms. As a result, utilizing probiotic microorganisms as therapeutics could be a potential possibility for arthritis treatment. This review highlights the known data on the therapeutic and preventative effects of probiotics in RA, as well as their interactions.
  10. Dihydroquinazolin-4(1H)-one derivatives as novel and potential leads for diabetic management
    Babatunde O, Hameed S, Salar U, Chigurupati S, Wadood A, Rehman AU, et al.
    Mol Divers, 2021 Mar 01.
    PMID: 33650031 DOI: 10.1007/s11030-021-10196-5
    A variety of dihydroquinazolin-4(1H)-one derivatives (1-37) were synthesized via "one-pot" three-component reaction scheme by treating aniline and different aromatic aldehydes with isatoic anhydride in the presence of acetic acid. Chemical structures of compounds were deduced by different spectroscopic techniques including EI-MS, HREI-MS, 1H-, and 13C-NMR. Compounds were subjected to α-amylase and α-glucosidase inhibitory activities. A number of derivatives exhibited significant to moderate inhibition potential against α-amylase (IC50 = 23.33 ± 0.02-88.65 ± 0.23 μM) and α-glucosidase (IC50 = 25.01 ± 0.12-89.99 ± 0.09 μM) enzymes, respectively. Results were compared with the standard acarbose (IC50 = 17.08 ± 0.07 μM for α-amylase and IC50 = 17.67 ± 0.09 μM for α-glucosidase). Structure-activity relationship (SAR) was rationalized by analyzing the substituents effects on inhibitory potential. Kinetic studies were implemented to find the mode of inhibition by compounds which revealed competitive inhibition for α-amylase and non-competitive inhibition for α-glucosidase. However, in silico study identified several important binding interactions of ligands (synthetic analogues) with the active site of both enzymes.
  11. 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.
  12. Fulltext Indole-3-acetamides: As Potential Antihyperglycemic and Antioxidant Agents; Synthesis, In Vitro α-Amylase Inhibitory Activity, Structure-Activity Relationship, and In Silico Studies
    Kanwal, Khan KM, Chigurupati S, Ali F, Younus M, Aldubayan M, et al.
    ACS Omega, 2021 Jan 26;6(3):2264-2275.
    PMID: 33521466 DOI: 10.1021/acsomega.0c05581
    Indole-3-acetamides (1-24) were synthesized via coupling of indole-3-acetic acid with various substituted anilines in the presence of coupling reagent 1,1-carbonyldiimidazole. The structures of synthetic molecules were elucidated through different spectroscopic techniques including electron ionization-mass spectroscopy (EI-MS), 1H-, 13C NMR, and high-resolution EI-MS (HREI-MS). These compounds were screened for their antihyperglycemic and antioxidant potentials. All compounds displayed good to moderate inhibition against α-amylase enzyme with IC50 values ranging between 1.09 ± 0.11 and 2.84 ± 0.1 μM compared to the standard acarbose (IC50 = 0.92 ± 0.4 μM). Compound 15 (IC50 = 1.09 ± 0.11 μM) was the most active compound of the series and exhibited good inhibition against α-amylase; in addition, this compound also exhibited good antioxidant potential with IC50 values of 0.35 ± 0.1 and 0.81 ± 0.25 μM in 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, respectively. The binding interactions of synthetic molecules with the enzyme's active site were confirmed via in silico studies. The current study had identified a number of lead molecules as potential antihyperglycemic and antioxidant agents.
  13. 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.
  14. Bacterial endosymbiont inhabiting Leucaena leucocephala leaves and their antioxidant and antidiabetic potential
    Chigurupati S, Vijayabalan S, Selvarajan KK, Alhowail A, Kauser F
    J Complement Integr Med, 2020 Dec 22;18(2):319-325.
    PMID: 34187119 DOI: 10.1515/jcim-2020-0203
    OBJECTIVES: Research on endosymbionts is emerging globally and is considered as a potential source of bioactive phytochemicals. The present study examines the antioxidant and antidiabetic of the endophytic crude extract isolated from Leucaena leucocephala leaves.

    METHODS: Endophytic bacteria were isolated from the leaves of L. leucocephala and 16S rRNA gene sequencing was used to establish their identity. The in vitro antioxidant effect of endophytic crude extract (LL) was evaluated using 2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) free radical scavenging methods. The in vitro antidiabetic properties of LL were evaluated using α-amylase and α-glucosidase enzyme inhibition assay.

    RESULTS: The isolated endophytic bacteria were identified as Cronobacter sakazakii. LL displayed potent free radical scavenging effect against ABTS and DPPH radicals with an inhibitory concentration 50% (IC50) value of 17.49 ± 0.06 and 11.3 ± 0.1 μg/mL respectively. LL exhibited α-amylase and α-glucosidase inhibition with an IC50 value of 23.3 ± 0.08 and 23.4 ± 0.1 μg/mL respectively compared to the standard drug (acarbose). Both glucose loaded normoglycemic rats and STZ induced diabetic rats treated with LL (200 mg/kg) exhibited a considerable reduction in blood glucose levels p<0.01 after 8 h of treatment when compared to normal and diabetic control rats respectively.

    CONCLUSIONS: Thus, the study shows that LL has a wellspring of natural source of antioxidants, and antidiabetic agents and phytoconstituents present in endophytes could be the rich source for bioactive compounds.

  15. Fulltext Structural elucidation, molecular docking, α-amylase and α-glucosidase inhibition studies of 5-amino-nicotinic acid derivatives
    Nawaz M, Taha M, Qureshi F, Ullah N, Selvaraj M, Shahzad S, et al.
    BMC Chem, 2020 Dec;14(1):43.
    PMID: 32685927 DOI: 10.1186/s13065-020-00695-1
    In this study, 5-amino-nicotinic acid derivatives (1-13) have been designed and synthesized to evaluate their inhibitory potential against α-amylase and α-glucosidase enzymes. The synthesized compounds (1-13) exhibited promising α-amylase and α-glucosidase activities. IC50 values for α-amylase activity ranged between 12.17 ± 0.14 to 37.33 ± 0.02 µg/mL ± SEM while for α-glucosidase activity the IC50 values were ranged between 12.01 ± 0.09 to 38.01 ± 0.12 µg/mL ± SEM. In particular, compounds 2 and 4-8 demonstrated significant inhibitory activities against α-amylase and α-glucosidase and the inhibitory potential of these compounds was comparable to the standard acarbose (10.98 ± 0.03 and 10.79 ± 0.17 µg/mL ± SEM, respectively). In addition, the impact of substituent on the inhibitory potential of these compounds was assessed to establish structure activity relationships. Studies in molecular simulations were conducted to better comprehend the binding properties of the compounds. All the synthesized compounds were extensively characterized with modern spectroscopic methods including 1H-NMR, 13C-NMR, FTIR, HR-MS and elemental analysis.
  16. Exploring efficacy of indole-based dual inhibitors for α-glucosidase and α-amylase enzymes: In silico, biochemical and kinetic studies
    Kawde AN, Taha M, Alansari RS, Almandil NB, Anouar EH, Uddin N, et al.
    Int J Biol Macromol, 2020 Jul 01;154:217-232.
    PMID: 32173438 DOI: 10.1016/j.ijbiomac.2020.03.090
    α-Glucosidase and α-amylase are enzymes which are associated with diabetic II. These enzymes break macromolecules of sugar into monosugar molecules which is soluble in body, hence increase the sugar level in blood. There is need to develop economical and save inhibitors to prevent them from breaking sugar macromolecules to soluble molecules which will control the level of sugar in blood. Therefore, we synthesized indole-based derivatives (1-18) and evaluated as dual inhibitor for α-glucosidase and α-amylase. These chemical scaffolds were built with variation in aryl ring which were found active with good to moderate activity for α-glucosidase having IC50 value ranging from 13.99 ± 0.10 to 59.09 ± 0.30 μM when compared with standard acarbose with IC50 of 11.29 ± 0.10 μM; for α-amylase IC50 value ranging from 13.14 ± 0.10 to 58.99 ± 0.30 μM when compared with the standard acarbose with IC50 of 11.12 ± 0.10 μM. Structure activity relationship (SAR) has been established for all compounds. Enzymatic kinetic study and molecular docking study have been carried out to investigate the binding interactions α-glucosidase and α-amylase enzyme.
  17. 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.
  18. Synthesis of new indazole based dual inhibitors of α-glucosidase and α-amylase enzymes, their in vitro, in silico and kinetics studies
    Rafique R, Khan KM, Arshia, Kanwal, Chigurupati S, Wadood A, et al.
    Bioorg Chem, 2020 01;94:103195.
    PMID: 31451297 DOI: 10.1016/j.bioorg.2019.103195
    The current study describes the discovery of novel inhibitors of α-glucosidase and α-amylase enzymes. For that purpose, new hybrid analogs of N-hydrazinecarbothioamide substituted indazoles 4-18 were synthesized and fully characterized by EI-MS, FAB-MS, HRFAB-MS, 1H-, and 13C NMR spectroscopic techniques. Stereochemistry of the imine double bond was established by NOESY measurements. All derivatives 4-18 with their intermediates 1-3, were evaluated for in vitro α-glucosidase and α-amylase enzyme inhibition. It is worth mentioning that all synthetic compounds showed good inhibition potential in the range of 1.54 ± 0.02-4.89 ± 0.02 µM for α-glucosidase and for α-amylase 1.42 ± 0.04-4.5 ± 0.18 µM in comparison with the standard acarbose (IC50 value of 1.36 ± 0.01 µM). In silico studies were carried out to rationalize the mode of binding interaction of ligands with the active site of enzymes. Moreover, enzyme inhibitory kinetic characterization was also performed to understand the mechanism of enzyme inhibition.
  19. Synthesis, in vitro α-amylase inhibitory, and radicals (DPPH & ABTS) scavenging potentials of new N-sulfonohydrazide substituted indazoles
    Rafique R, Khan KM, Arshia, Chigurupati S, Wadood A, Rehman AU, et al.
    Bioorg Chem, 2020 01;94:103410.
    PMID: 31732193 DOI: 10.1016/j.bioorg.2019.103410
    Over-expression of α-amylase enzyme causes hyperglycemia which lead to many physiological complications including oxidative stress, one of the most commonly associated problem with diabetes mellitus. Marketed α-amylase inhibitors such as acarbose, voglibose, and miglitol used to treat type-II diabetes mellitus, but also linked to several harmful effects. Therefore, it is essential to explore new and nontoxic antidiabetic agents with additional antioxidant properties. In this connection, a series of new N-sulfonohydrazide substituted indazoles 1-19 were synthesized by multistep reaction scheme and assessed for in vitro α-amylase inhibitory and radical (DPPH and ABTS) scavenging properties. All compounds were fully characterized by different spectroscopic techniques including 1H, 13C NMR, EI-MS, HREI-MS, ESI-MS, and HRESI-MS. Compounds showed promising α-amylase inhibitory activities (IC50 = 1.23 ± 0.06-4.5 ± 0.03 µM) as compared to the standard acarbose (IC50 1.20 ± 0.09 µM). In addition to that all derivatives were found good to moderate scavengers of DPPH (IC50 2.01 ± 0.13-5.3 ± 0.11) and ABTS (IC50 = 2.34 ± 0.07-5.5 ± 0.07 µM) radicals, in comparison with standard ascorbic acid having scavenging activities with IC50 = 1.99 ± 0.09 µM, and IC50 2.03 ± 0.11 µM for DPPH and ABTS radicals. In silico molecular docking study was conducted to rationalize the binding interaction of α-amylase enzyme with ligands. Compounds were observed as mixed type inhibitors in enzyme kinetic characterization.
  20. Antimicrobial Exploration Between Counterpart Endosymbiont and Host Plant (Tamarindus indica Linn.)
    Chigurupati S, Vijayabalan S, Selvarajan KK, Aldubayan M, Alhowail A, Mani V, et al.
    Curr Pharm Biotechnol, 2020;21(5):384-389.
    PMID: 31657678 DOI: 10.2174/1389201020666191028105325
    BACKGROUND: Endophytic bacteria produce various bioactive secondary metabolites, which benefit human health. Tamarindus indica L. is well known for its medicinal value in human health care. Several studies have reported on its biological effects from various parts of T. indica, but only a few studies have been devoted to examining the biological activity of endophytes of T. indica.

    OBJECTIVES: In the present study, an endophyte was isolated from the leaves of T. indica and screened for its antimicrobial potential.

    METHODS: The selected endophyte was identified by 16s rRNA partial genome sequencing and investigated for their antimicrobial potency. The preliminary phytochemical tests were conducted for the affirmation of phytoconstituents in the endophytic crude ethyl acetate extract of T. indica (TIM) and total phenolic content was performed. The antimicrobial potential of TIM was evaluated against human pathogenic ATCC gram-positive and gram-negative bacterial strains.

    RESULTS: TIM exhibited an appreciable amount of gallic acid equivalent phenolic content (21.6 ± 0.04 mg GAE/g of crude extract). TIM showed the Minimum Inhibitory Concentration (MIC) at 250 μg/mL and Minimum Bactericidal Concentration (MBC) at 500 μg/mL among the selected human pathogenic ATCC strains. At MIC of 500 μg/mL, TIM displayed a significant zone of inhibition against P. aeruginosa and N. gonorrhoeae.

    CONCLUSION: The results from our study highlighted for the first time the antimicrobial potential of endophytic bacterial strain Bacillus velezensis in T. indica leaves and it could be further explored as a source of natural antimicrobial agents.

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