Displaying publications 1 - 20 of 42 in total

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  1. Synthesis, α-amylase inhibitory potential and molecular docking study of indole derivatives
    Taha M, Baharudin MS, Ismail NH, Imran S, Khan MN, Rahim F, et al.
    Bioorg Chem, 2018 10;80:36-42.
    PMID: 29864686 DOI: 10.1016/j.bioorg.2018.05.021
    In search of potent α-amylase inhibitor we have synthesized eighteen indole analogs (1-18), characterized by NMR and HR-EIMS and screened for α-amylase inhibitory activity. All analogs exhibited a variable degree of α-amylase inhibition with IC50 values ranging between 2.031 ± 0.11 and 2.633 ± 0.05 μM when compared with standard acarbose having IC50 values 1.927 ± 0.17 μM. All compounds showed good α-amylase inhibition. Compound 14 was found to be the most potent analog among the series. Structure-activity relationship has been established for all compounds mainly based on bringing about the difference of substituents on phenyl ring. To understand the binding interaction of the most active analogs molecular docking study was performed.
  2. 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.
  3. 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.
  4. 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.
  5. Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies
    Chigurupati S, Selvaraj M, Mani V, Selvarajan KK, Mohammad JI, Kaveti B, et al.
    Bioorg Chem, 2016 08;67:9-17.
    PMID: 27231830 DOI: 10.1016/j.bioorg.2016.05.002
    The synthesis of novel indolopyrazoline derivatives (P1-P4 and Q1-Q4) has been characterized and evaluated as potential anti-Alzheimer agents through in vitro Acetylcholinesterase (AChE) inhibition and radical scavenging activity (antioxidant) studies. Specifically, Q3 shows AChE inhibition (IC50: 0.68±0.13μM) with strong DPPH and ABTS radical scavenging activity (IC50: 13.77±0.25μM and IC50: 12.59±0.21μM), respectively. While P3 exhibited as the second most potent compound with AChE inhibition (IC50: 0.74±0.09μM) and with DPPH and ABTS radical scavenging activity (IC50: 13.52±0.62μM and IC50: 13.13±0.85μM), respectively. Finally, molecular docking studies provided prospective evidence to identify key interactions between the active inhibitors and the AChE that furthermore led us to the identification of plausible binding mode of novel indolopyrazoline derivatives. Additionally, in-silico ADME prediction using QikProp shows that these derivatives fulfilled all the properties of CNS acting drugs. This study confirms the first time reporting of indolopyrazoline derivatives as potential anti-Alzheimer agents.
  6. Chalcones and bis-chalcones: As potential α-amylase inhibitors; synthesis, in vitro screening, and molecular modelling studies
    Tajudeen Bale A, Mohammed Khan K, Salar U, Chigurupati S, Fasina T, Ali F, et al.
    Bioorg Chem, 2018 09;79:179-189.
    PMID: 29763804 DOI: 10.1016/j.bioorg.2018.05.003
    Despite of a diverse range of biological activities associated with chalcones and bis-chalcones, they are still neglected by the medicinal chemist for their possible α-amylase inhibitory activity. So, the current study is based on the evaluation of this class for the identification of new leads as α-amylase inhibitors. For that purpose, a library of substituted chalcones 1-13 and bis-chalcones 14-18 were synthesized and characterized by spectroscopic techniques EI-MS and 1H NMR. CHN analysis was carried out and found in agreement with the calculated values. All compounds were evaluated for in vitro α-amylase inhibitory activity and demonstrated good activities in the range of IC50 = 1.25 ± 1.05-2.40 ± 0.09 µM as compared to the standard acarbose (IC50 = 1.04 ± 0.3 µM). Limited structure-activity relationship (SAR) was established by considering the effect of different groups attached to aryl rings on varying inhibitory activity. SMe group in chalcones and OMe group in bis-chalcones were found more influential on the activity than other groups. However, in order to predict the involvement of different groups in the binding interactions with the active site of α-amylase enzyme, in silico studies were also conducted.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. New Hybrid Scaffolds based on Hydrazinyl Thiazole Substituted Coumarin; As Novel Leads of Dual Potential; In Vitro α-Amylase Inhibitory and Antioxidant (DPPH and ABTS Radical Scavenging) Activities
    Salar U, Khan KM, Chigurupati S, Syed S, Vijayabalan S, Wadood A, et al.
    Med Chem, 2019;15(1):87-101.
    PMID: 30179139 DOI: 10.2174/1573406414666180903162243
    BACKGROUND: Despite many side effects associated, there are many drugs which are being clinically used for the treatment of type-II diabetes mellitus (DM). In this scenario, there is still need to develop new therapeutic agents with more efficacy and less side effects. By keeping in mind the diverse spectrum of biological potential associated with coumarin and thiazole, a hybrid class based on these two heterocycles was synthesized.

    METHOD: Hydrazinyl thiazole substituted coumarins 4-20 were synthesized via two step reaction. First step was the acid catalyzed reaction of 3-formyl/acetyl coumarin derivatives with thiosemicarbazide to form thiosemicarbazone intermediates 1-3, followed by the reaction with different phenacyl bromides to afford products 4-20. All the synthetic analogs 4-20 were characterized by different spectroscopic techniques such as EI-MS, HREI-MS, 1H-NMR and 13C-NMR. Stereochemical assignment of the iminic double bond was carried out by the NOESY experiments. Elemental analysis was found in agreement with the calculated values.

    RESULTS: Compounds 4-20 were screened for α-amylase inhibitory activity and showed good activity in the range of IC50 = 1.829 ± 0.102-3.37 ± 0.17 µM as compared to standard acarbose (IC50 = 1.819 ± 0.19 µM). Compounds were also investigated for their DPPH and ABTS radical scavenging activities and displayed good radical scavenging potential. In addition to that molecular modelling study was conducted on all compounds to investigate the interaction details of compounds 4- 20 (ligands) with active site (receptor) of enzyme.

    CONCLUSION: The newly identified hybrid class may serve as potential lead candidates for the management of diabetes mellitus.

  13. 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.
  14. Fulltext New Hybrid Hydrazinyl Thiazole Substituted Chromones: As Potential α-Amylase Inhibitors and Radical (DPPH & ABTS) Scavengers
    Salar U, Khan KM, Chigurupati S, Taha M, Wadood A, Vijayabalan S, et al.
    Sci Rep, 2017 12 05;7(1):16980.
    PMID: 29209017 DOI: 10.1038/s41598-017-17261-w
    Current research is based on the identification of novel inhibitors of α-amylase enzyme. For that purpose, new hybrid molecules of hydrazinyl thiazole substituted chromones 5-27 were synthesized by multi-step reaction and fully characterized by various spectroscopic techniques such as EI-MS, HREI-MS, 1H-NMR and 13C-NMR. Stereochemistry of the iminic bond was confirmed by NOESY analysis of a representative molecule. All compounds 5-27 along with their intervening intermediates 1-4, were screened for in vitro α-amylase inhibitory, DPPH and ABTS radical scavenging activities. All compounds showed good inhibition potential in the range of IC50 = 2.186-3.405 µM as compared to standard acarbose having IC50 value of 1.9 ± 0.07 µM. It is worth mentioning that compounds were also demonstrated good DPPH (IC50 = 0.09-2.233 µM) and ABTS (IC50 = 0.584-3.738 µM) radical scavenging activities as compared to standard ascorbic acid having IC50 = 0.33 ± 0.18 µM for DPPH and IC50 = 0.53 ± 0.3 µM for ABTS radical scavenging activities. In addition to that cytotoxicity of the compounds were checked on NIH-3T3 mouse fibroblast cell line and found to be non-toxic. In silico studies were performed to rationalize the binding mode of compounds (ligands) with the active site of α-amylase enzyme.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. Synthesis and biological evaluation of indole derivatives as α-amylase inhibitor
    Imran S, Taha M, Selvaraj M, Ismail NH, Chigurupati S, Mohammad JI
    Bioorg Chem, 2017 08;73:121-127.
    PMID: 28648924 DOI: 10.1016/j.bioorg.2017.06.007
    A series of twenty indole hydrazone analogs (1-21) were synthesized, characterized by different spectroscopic techniques such as 1H NMR and EI-MS, and screened for α-amylase inhibitory activity. All analogs showed a variable degree of α-amylase inhibition with IC50 values ranging between 1.66 and 2.65μM. Nine compounds that are 1 (2.23±0.01μM), 8 (2.44±0.12μM), 10 (1.92±0.12μM), 12 (2.49±0.17μM), 13 (1.66±0.09μM), 17 (2.25±0.1μM), 18 (1.87±0.25μM), 20 (1.83±0.63μM), and 19 (1.97±0.02μM) showed potent α-amylase inhibition when compared with the standard acarbose (1.05±0.29μM). Other analogs showed good to moderate α-amylase inhibition. The structure activity relationship is mainly focusing on difference of substituents on phenyl part. Molecular docking studies were carried out to understand the binding interaction of the most active compounds.
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