Displaying publications 1 - 20 of 42 in total

  1. Bera H, Chigurupati S
    Eur J Med Chem, 2016 Nov 29;124:992-1003.
    PMID: 27783978 DOI: 10.1016/j.ejmech.2016.10.032
    Thymidine phosphorylase (TP, EC, an enzyme involved in pyrimidine salvage pathway, is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and gliostatin. It is extremely upregulated in a variety of solid tumours. The TP amplification is associated with concomitant overexpression of many angiogenic factors such as matrix metalloproteases (MMPs), interleukins (ILs), vascular endothelial growth factor (VEGF) etc., resulting in promotion of angiogenesis and cancer metastasis. In addition, overshooting TP level protects tumour cells from apoptosis and helps cell survival. Thus, TP is identified as a prime target for developing novel anticancer therapies. Pioneering research activities investigated a large number of TP inhibitors, most of which are pyrimidine or purine analogues. Recently, an array of structurally diverse non-nucleobase derivatives was designed, synthesized and established as promising TP inhibitors. This review, following an outline on the TP structure and functions, gives an overview of the recent advancement of various non-nucleobase TP inhibitors as novel anti-cancer agents.
  2. Chigurupati S, Dhanaraj SA, Balakumar P
    Eur J Pharmacol, 2015 May 15;755:50-7.
    PMID: 25748601 DOI: 10.1016/j.ejphar.2015.02.043
    Described since long as a member of the nuclear receptor superfamily, peroxisome proliferator-activated receptors (PPARs) regulate the gene expression of proteins involved in glucose and lipid metabolism. PPARs indeed regulate several physiologic processes, including lipid homeostasis, adipogenesis, inflammation, and wound healing. PPARs bind natural or synthetic PPAR ligands can function as cellular sensors to regulate the gene transcription. Dyslipidemia, and type 2 diabetes mellitus (T2DM) with insulin resistance are treated using agonists of PPARα and PPARγ, respectively. The PPARγ is a key regulator of insulin sensitization and glucose metabolism, and therefore is considered as an imperative pharmacological target to combat diabetic metabolic disease and insulin resistance. Of note, currently available PPARγ full agonists like rosiglitazone display serious adverse effects such as fluid retention/oedema, weight gain, and increased incidence of cardiovascular events. On the other hand, PPARγ partial agonists are being suggested to devoid or having less incidence of these undesirable events, and are under developmental stages. Current research is on the way for the development of novel PPARγ partial agonists with enhanced therapeutic efficacy and reduced adverse effects. This review sheds lights on the current status of development of PPARγ partial agonists, for the management of T2DM, having comparatively less or no adverse effects to that of PPARγ full agonists.
  3. Islam MJ, Roshid B, Pervin S, Kabir S, Chigurupati S, Hasan MN
    Mymensingh Med J, 2019 Apr;28(2):484-489.
    PMID: 31086172
    Approximately 80% ovarian tumors are benign, and these arise mostly in young adult females. Malignant tumors are more prevalent in ageing women, between the ages of 45-65 years. Mucinous ovarian cancer represents about 5% of epithelial ovarian cancers (EOC). We have reported a case of mucinous cystadenocarcinoma in 35-year-old lady with metastasis to momentum. Imaging (Radiograph & CT scan) studies showed a large right sided pelvic mass with probable origin in the right ovary. Cancer antigen-125 was elevated, while carcinoembrionic antigen and alpha-fetoprotein were normal. Mutational profiles shown distinct finding, as KRAS mutations positive nevertheless p53 and BRCA mutations are absent. She had undergone total abdominal hysterectomy with bilateral salphingo-oopherectomy along with pelvic dissection for removal of lymph nodes at the age of 35. She was given 3 cycles of chemotherapy with cisplatin and paclitaxel. To the best of our knowledge, this is the one of the little cases of ovarian mucinous cystadenocarcinoma being reported at a relatively young age and the first case being reported from Bangladesh.
  4. 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.

  5. Appala RN, Chigurupati S, Appala RV, Krishnan Selvarajan K, Islam Mohammad J
    Scientifica (Cairo), 2016;2016:6897890.
    PMID: 27127683 DOI: 10.1155/2016/6897890
    A highly sensitive and simple HPLC-UV method was developed and validated for the assay of glutathione (GSH) in PC-12 cells. Glutathione is a major intracellular antioxidant having multiple biological effects, best known for its cytoprotective effects against cell damage from reactive oxygen species and toxic reactive metabolites and regulating the cellular redox homeostasis. Due to its own sulfhydryl (SH) group, GSH readily reacts with Ellman's reagent to form a stable dimer which allows for quantitative estimation of GSH in biological systems by UV detection. The separation was achieved using a C8 column with a mobile phase consisting of phosphate buffer adjusted to pH 2.5 (mobile phase A) and acetonitrile (mobile phase B), running in a segmented gradient manner at a flow rate of 0.8 mL/min, and UV detection was performed at 280 nm. The developed HPLC-UV method was validated with respect to precision, accuracy, robustness, and linearity within a range of 1-20 μg/mL. Limit of detection (LOD) and limit of quantification (LOQ) were 0.05 and 0.1 μg/mL, respectively. Furthermore, the method shows the applicability for monitoring the oxidative stress in PC-12 cells.
  6. 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.
  7. 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.

  8. 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.

  9. 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. 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.
  11. Taha M, Irshad M, Imran S, Chigurupati S, Selvaraj M, Rahim F, et al.
    Eur J Med Chem, 2017 Dec 01;141:530-537.
    PMID: 29102178 DOI: 10.1016/j.ejmech.2017.10.028
    Piperazine Sulfonamide analogs (1-19) have been synthesized, characterized by different spectroscopic techniques and evaluated for α-amylase Inhibition. Analogs 1-19 exhibited a varying degree of α-amylase inhibitory activity with IC50 values ranging in between 1.571 ± 0.05 to 3.98 ± 0.397 μM when compared with the standard acarbose (IC50 = 1.353 ± 0.232 μM). Compound 1, 2, 3 and 7 showed significant inhibitory effects with IC50 value 2.348 ± 0.444, 2.064 ± 0.04, 1.571 ± 0.05 and 2.118 ± 0.204 μM, respectively better than the rest of the series. Structure activity relationships were established. Molecular docking studies were performed to understand the binding interaction of the compounds.
  12. 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.
  13. 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.
  14. 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.
  15. Hameed S, Kanwal, Seraj F, Rafique R, Chigurupati S, Wadood A, et al.
    Eur J Med Chem, 2019 Dec 01;183:111677.
    PMID: 31514061 DOI: 10.1016/j.ejmech.2019.111677
    Benzotriazoles (4-6) were synthesized which were further reacted with different substituted benzoic acids and phenacyl bromides to synthesize benzotriazole derivatives (7-40). The synthetic compounds (7-40) were characterized via different spectroscopic techniques including EI-MS, HREI-MS, 1H-, and 13C NMR. These molecules were examined for their anti-hyperglycemic potential hence were evaluated for α-glucosidase and α-amylase inhibitory activities. All benzotriazoles displayed moderate to good inhibitory activity in the range of IC50 values of 2.00-5.6 and 2.04-5.72 μM against α-glucosidase and α-amylase enzymes, respectively. The synthetic compounds were divided into two categories "A" and "B", in order to understand the structure-activity relationship. Compounds 25 (IC50 = 2.41 ± 1.31 μM), (IC50 = 2.5 ± 1.21 μM), 36 (IC50 = 2.12 ± 1.35 μM), (IC50 = 2.21 ± 1.08 μM), and 37 (IC50 = 2.00 ± 1.22 μM), (IC50 = 2.04 ± 1.4 μM) with chloro substitution/s at aryl ring were found to be most active against α-glucosidase and α-amylase enzymes. Molecular docking studies on all compounds were performed which revealed that chloro substitutions are playing a pivotal role in the binding interactions. The enzyme inhibition mode was also studied and the kinetic studies revealed that the synthetic molecules have shown competitive mode of inhibition against α-amylase and non-competitive mode of inhibition against α-glucosidase enzyme.
  16. 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.
  17. 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.
  18. 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. 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.
  20. 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.
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