Displaying publications 1 - 20 of 42 in total

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  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.

  10. 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.

  11. 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.
  12. 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.
  13. 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.
  14. 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.

  15. 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.
  16. 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.
  17. 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.
  18. 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 2.4.2.4), 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.
  19. 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.
  20. 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.
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