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Synthesis, β-glucuronidase inhibition and molecular docking studies of cyano-substituted bisindole hydrazone hybrids

Abid O, Imran S, Taha M, Ismail NH, Jamil W, Kashif SM, et al.

Mol Divers, 2021 May;25(2):995-1009.
PMID: 32301032 DOI: 10.1007/s11030-020-10084-4

The β-glucuronidase, a lysosomal enzyme, catalyzes the cleavage of glucuronosyl-O-bonds. Its inhibitors play a significant role in different medicinal therapies as they cause a decrease in carcinogen-induced colonic tumors by reducing the level of toxic substances present in the intestine. Among those inhibitors, bisindole derivatives had displayed promising β-glucuronidase inhibition activity. In the current study, hydrazone derivatives of bisindolymethane (1-30) were synthesized and evaluated for in vitro β-glucuronidase inhibitory activity. Twenty-eight analogs demonstrated better activity (IC50 = 0.50-46.5 µM) than standard D-saccharic acid 1,4-lactone (IC50 = 48.4 ± 1.25 µM). Compounds with hydroxyl group like 6 (0.60 ± 0.01 µM), 20 (1.50 ± 0.10 µM) and 25 (0.50 ± 0.01 µM) exhibited the most potent inhibitory activity, followed by analogs with fluorine 21 (3.50 ± 0.10 µM) and chlorine 23 (8.20 ± 0.20 µM) substituents. The presence of hydroxyl group at the aromatic side chain was observed as the main contributing factor in the inhibitory potential. From the docking studies, it was predicted that the active compounds can fit properly in the binding groove of the β-glucuronidase and displayed significant binding interactions with essential residues.

Matched MeSH terms: Glucuronidase/antagonists & inhibitors
Microwave-assisted extraction of polysaccharides from Micromelum minutum leaves using citric acid monohydrate-glycerol based deep eutectic solvents and evaluation of biological activities

Md Yusoff MH, Shafie MH

Anal Chim Acta, 2024 Dec 01;1331:343351.
PMID: 39532430 DOI: 10.1016/j.aca.2024.343351

BACKGROUND: The extraction of polysaccharides using an acidic extraction media has been extensively reported, highlighting its effectiveness in yielding high-quality polysaccharides. A higher concentration of acidic solution could hydrolyze the structure of polysaccharide, while a low concentration reduces the extraction efficiency. Despite this challenges, deep eutectic solvents (DES) were introduced as an alternative extraction medium due to additional interactions such as inter and intra-molecular interactions, Van de Waals, hydrogen bond, and electrostatic interactions, which could improve the polysaccharide extraction efficiency and biological activities. Furthermore, the extraction conditions such as extraction medium and extraction parameters could affect the properties of polysaccharides as well as influence their structure-activity relationship for biological activities.
RESULTS: The result showed that the microwave-assisted extraction of Micromelum minutum leaf polysaccharide (MMLP) using DES as an extraction media (MMLP-DES) gave a higher yield (improvement of 101.20 %) than citric acid monohydrate (CAM) (MMLP-CAM) and required a lower percentage of microwave power (19.83 % less) and time (0.78 min less). The properties of MMLPs significantly differ based on their pH, molecular weight, viscosity, degree of esterification and monosaccharide molar ratio which influenced the biological activities. Compared to MMLP-CAM, MMLP-DES had a more branched and less linear structure. The bioactivities study revealed that MMLP-DES exhibited higher antioxidant and anti-α-amylase activities (i.e.
, DPPH: 74.52 %, FRAP: 2.87 mM FeSO4 and α-amylase inhibition: 86.23 %) compared to MMLP-CAM (i.e.
, DPPH: 49.33 %, FRAP: 1.49 mM FeSO4, and α-amylase inhibition: 81.76 %). The mechanism and structure-activity relationship of MMLPs on bioactivities were also hypothesized.
SIGNIFICANCE: Based on our previous study, the citric acid monohydrate-glycerol based DES as an extraction medium has enhanced the extraction yield of polysaccharides from M. minutum. This study highlights the DES combined with microwave-assisted extraction to improve the yield of MMLP and evaluate the biological activities compared to CAM as a classical solvent. In conclusion, the DES showed the advantages for extraction of polysaccharides with desired biological activities.

Matched MeSH terms: alpha-Amylases/antagonists & inhibitors; Biphenyl Compounds/antagonists & inhibitors
Rapid characterisation of xanthine oxidase inhibitors from the flowers of Chrysanthemum morifolium Ramat. Using metabolomics approach

Loh KE, Chin YS, Safinar Ismail I, Tan HY

Phytochem Anal, 2022 Jan;33(1):12-22.
PMID: 34000756 DOI: 10.1002/pca.3057

INTRODUCTION: Hyperuricemia is the key risk factor for gout, in which the elevated uric acid is attributed to the oxidation of hypoxanthine and xanthine to uric acid by xanthine oxidase (XO). Adverse effects of the current treatments lead to an urgent need for safer and more effective alternative from natural resources.
OBJECTIVE: To compare the metabolite profile of Chrysanthemum morifolium flower fraction with that of its detannified fraction in relation to XO inhibitory activity using a rapid and effective metabolomics approach.
METHODS: Proton nuclear magnetic resonance (1 H-NMR)-based metabolomics approach coupled with multivariate data analysis was utilised to characterise the XO inhibitors related to the antioxidant properties, total phenolic, and total flavonoid contents of the C. morifolium dried flowers.
RESULTS: The highest XO inhibitory activity, 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity, total phenolic and flavonoid content with strong positive correlation between them were observed in the ethyl acetate (EtOAc) fraction. Detannified EtOAc showed higher XO inhibitory activity than non-detannified EtOAc fraction. A total of 17 metabolites were tentatively identified, of which three namely kaempferol, 4-hydroxybenzoic acid and apigenin, could be suggested to be responsible for the strong XO inhibitory activity. Additive interaction between 4-hydroxybenzoic acid and apigenin (or kaempferol) in XO inhibition was demonstrated in the interaction assay conducted.
CONCLUSION: Chrysanthemum morifolium dried flower-part could be further explored as a natural XO inhibitor for its anti-hyperuricemic potential. Metabolomics approach served as an effective classification of plant metabolites responsible for XO inhibitory activity, and demonstrated that multiple active compounds can work additively in giving combined inhibitory effects.

Matched MeSH terms: Xanthine Oxidase/antagonists & inhibitors*
Targeting cancer via Golgi α-mannosidase II inhibition: How far have we come in developing effective inhibitors?

Lee ZY, Loo JSE, Wibowo A, Mohammat MF, Foo JB

Carbohydr Res, 2021 Oct;508:108395.
PMID: 34280804 DOI: 10.1016/j.carres.2021.108395

Dysregulation of glycosylation pathways has been well documented in several types of cancer, where it often participates in cancer development and progression, especially cancer metastasis. Hence, inhibition of glycosidases such as mannosidases can disrupt the biosynthesis of glycans on cell surface glycoproteins and modify their role in carcinogenesis and metastasis. Several reviews have delineated the role of N-glycosylation in cancer, but the data regarding effective inhibitors remains sparse. Golgi α-mannosidase has been an attractive therapeutic target for preventing the formation of ß1,6-branched complex type N-glycans. However, due to its high structural similarity to the broadly specific lysosomal α-mannosidase, undesired co-inhibition occurs and this leads to serious side effects that complicates its potential role as a therapeutic agent. Even though extensive efforts have been geared towards the discovery of effective inhibitors, no breakthrough has been achieved thus far which could allow for their use in clinical settings. Improving the specificity of current inhibitors towards Golgi α-mannosidase is requisite in progressing this class of compounds in cancer chemotherapy. In this review, we highlight a few potent and selective inhibitors discovered up to the present to guide researchers for rational design of further effective inhibitors to overcome the issue of specificity.

Matched MeSH terms: alpha-Mannosidase/antagonists & inhibitors
Fulltext Final Results of RIGHT Choice: Ribociclib Plus Endocrine Therapy Versus Combination Chemotherapy in Premenopausal Women With Clinically Aggressive Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer

Lu YS, Mahidin EIBM, Azim H, Eralp Y, Yap YS, Im SA, et al.

J Clin Oncol, 2024 Aug 10;42(23):2812-2821.
PMID: 38771995 DOI: 10.1200/JCO.24.00144

PURPOSE: A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC).
METHODS: In this open-label, multicenter, randomized phase II trial, pre/perimenopausal women with clinically aggressive HR+/HER2- ABC were randomly assigned 1:1 to first-line ribociclib (600 mg once daily; 3 weeks on, 1 week off) plus letrozole/anastrozole and goserelin or investigator's choice of combination CT (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary end point was progression-free survival (PFS).
RESULTS: Among 222 patients randomly assigned to ribociclib plus ET (n = 112) or combination CT (n = 110), 150 (67.6%) had symptomatic visceral metastases, 41 (18.5%) had rapid disease progression per investigator's judgment, and 31 (14.0%) had symptomatic nonvisceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. The median follow-up time was 37.0 months. At data cutoff, 31.3% (ribociclib arm) and 15.5% (CT arm) of patients had completed study treatment and transitioned to post-trial access. The median PFS was 21.8 months (ribociclib plus ET; [95% CI, 17.4 to 26.7]) and 12.8 months (combination CT; [95% CI, 10.1 to 18.4); hazard ratio, 0.61 [95% CI, 0.43 to 0.87]; P = .003. The overall response rates and the median time to response in the ribociclib versus CT arms, respectively, were 66.1% and 61.8% and 4.9 months and 3.2 months (hazard ratio, 0.76 [95% CI, 0.55 to 1.06]). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm.
CONCLUSION: First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients with clinically aggressive HR+/HER2- ABC.

Matched MeSH terms: Cyclin-Dependent Kinase 4/antagonists & inhibitors
Aducanumab in Alzheimer's Disease: A Critical Update

Ashique S, Sirohi E, Kumar S, Rihan M, Mishra N, Bhatt S, et al.

Curr Med Chem, 2024;31(31):5004-5026.
PMID: 37497712 DOI: 10.2174/0929867331666230727103553

Alzheimer's disease (AD) is a complex neurological disorder that results in cognitive decline. The incidence rates of AD have been increasing, particularly among individuals 60 years of age or older. In June 2021, the US FDA approved aducanumab, the first humanized monoclonal antibody, as a potential therapeutic option for AD. Clinical trials have shown this drug to effectively target the accumulation of Aβ (beta-amyloid) plaques in the brain, and its effectiveness is dependent on the dosage and duration of treatment. Additionally, aducanumab has been associated with improvements in cognitive function. Biogen, the pharmaceutical company responsible for developing and marketing aducanumab, has positioned it as a potential breakthrough for treating cerebral damage in AD. However, the drug has raised concerns due to its high cost, limitations, and potential side effects. AD is a progressive neurological condition that affects memory, cognitive function, and behaviour. It significantly impacts the quality of life of patients and caregivers and strains healthcare systems. Ongoing research focuses on developing disease-modifying therapies that can halt or slow down AD progression. The pathogenesis of AD involves various molecular cascades and signaling pathways. However, the formation of extracellular amyloid plaques is considered a critical mechanism driving the development and progression of the disease. Aducanumab, as a monoclonal antibody, has shown promising results in inhibiting amyloid plaque formation, which is the primary pathological feature of AD. This review explores the signaling pathways and molecular mechanisms through which aducanumab effectively prevents disease pathogenesis in AD.

Matched MeSH terms: Amyloid beta-Peptides/antagonists & inhibitors
A synthetic hydroxypropenone inhibits nitric oxide, prostaglandin E2, and proinflammatory cytokine synthesis

Liew CY, Tham CL, Lam KW, Mohamad AS, Kim MK, Cheah YK, et al.

Immunopharmacol Immunotoxicol, 2010 Sep;32(3):495-506.
PMID: 20109039 DOI: 10.3109/08923970903575708

HMP [3-(2-hydroxyphenyl)-1-(5-methyl-furan-2-y-l) propenone] was evaluated for its ability to inhibit the synthesis of major proinflammatory mediators and cytokines in interferon-gamma (IFN-gamma)- and lipopolysaccharide (LPS)-induced RAW 264.7 cells and phorbol myristate acetate (PMA)-differentiated/LPS-induced U937 cells. HMP suppressed the production of nitric oxide (NO) with significant inhibitory effects at doses as low as 0.78 microM (P < 0.05). Prostaglandin E2 (PGE2) secretion was also inhibited at doses of 12.5 microM and above (P < 0.01). The secretion of both TNF-alpha and IL-6 were only inhibited at the highest dose used (25 microM; P < 0.001). IL-1beta secretion was also inhibited from 12.5 microM onwards (P < 0.01). This inhibition was demonstrated to be caused by down-regulation of inducible enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), without direct effect upon iNOS or COX-2 enzyme activity. HMP only inhibited iNOS (P < 0.001) and IL-1beta (P < 0.05) gene expression at the highest tested concentration. HMP did not affect the secretion of chemokines IL-8 and monocyte chemotactic protein-1 (MCP-1) and the anti-inflammatory cytokine IL-10. The most striking effect of HMP was its NO inhibitory activity and therefore we conclude that HMP is a selective inhibitor of iNOS.

Matched MeSH terms: Interferon-gamma/antagonists & inhibitors; Nitric Oxide/antagonists & inhibitors*; Tumor Necrosis Factor-alpha/antagonists & inhibitors; Dinoprostone/antagonists & inhibitors*; Interleukin-6/antagonists & inhibitors; Cytokines/antagonists & inhibitors*; Interferon-alpha/antagonists & inhibitors; Nitric Oxide Synthase Type II/antagonists & inhibitors; Interleukin-1beta/antagonists & inhibitors
Fulltext Zerumbone Ameliorates Neuropathic Pain Symptoms via Cannabinoid and PPAR Receptors Using In Vivo and In Silico Models

Chia JSM, Farouk AAO, Mohamad TAST, Sulaiman MR, Zakaria H, Hassan NI, et al.

Molecules, 2021 Jun 24;26(13).
PMID: 34202590 DOI: 10.3390/molecules26133849

Neuropathic pain is a chronic pain condition persisting past the presence of any noxious stimulus or inflammation. Zerumbone, of the Zingiber zerumbet ginger plant, has exhibited anti-allodynic and antihyperalgesic effects in a neuropathic pain animal model, amongst other pharmacological properties. This study was conducted to further elucidate the mechanisms underlying zerumbone's antineuropathic actions. Research on therapeutic agents involving cannabinoid (CB) and peroxisome proliferator-activated receptors (PPARs) is rising. These receptor systems have shown importance in causing a synergistic effect in suppressing nociceptive processing. Behavioural responses were assessed using the von Frey filament test (mechanical allodynia) and Hargreaves plantar test (thermal hyperalgesia), in chronic constriction injury (CCI) neuropathic pain mice. Antagonists SR141716 (CB1 receptor), SR144528 (CB2 receptor), GW6471 (PPARα receptor) and GW9662 (PPARγ receptor) were pre-administered before the zerumbone treatment. Our findings indicated the involvement of CB1, PPARα and PPARγ in zerumbone's action against mechanical allodynia, whereas only CB1 and PPARα were involved against thermal hyperalgesia. Molecular docking studies also suggest that zerumbone has a comparable and favourable binding affinity against the respective agonist on the CB and PPAR receptors studied. This finding will contribute to advance our knowledge on zerumbone and its significance in treating neuropathic pain.

Matched MeSH terms: Receptor, Cannabinoid, CB1/antagonists & inhibitors*; Receptor, Cannabinoid, CB2/antagonists & inhibitors*; PPAR alpha/antagonists & inhibitors*; PPAR gamma/antagonists & inhibitors*
Fulltext Phenoxyacetohydrazide Schiff bases: β-glucuronidase inhibitors

Jamil W, Perveen S, Shah SA, Taha M, Ismail NH, Perveen S, et al.

Molecules, 2014 Jun 25;19(7):8788-802.
PMID: 24968334 DOI: 10.3390/molecules19078788

Phenoxyacetohydrazide Schiff base analogs 1-28 have been synthesized and their in vitro β-glucouoronidase inhibition potential studied. Compounds 1 (IC50=9.20±0.32 µM), 5 (IC50=9.47±0.16 µM), 7 (IC50=14.7±0.19 µM), 8 (IC50=15.4±1.56 µM), 11 (IC50=19.6±0.62 µM), 12 (IC50=30.7±1.49 µM), 15 (IC50=12.0±0.16 µM), 21 (IC50=13.7±0.40 µM) and 22 (IC50=22.0±0.14 µM) showed promising β-glucuronidase inhibition activity, better than the standard (D-saccharic acid-1,4-lactone, IC50=48.4±1.25 µM).

Matched MeSH terms: Glucuronidase/antagonists & inhibitors*
Synthesis and in vitro urease inhibitory activity of N,N'-disubstituted thioureas

Khan KM, Naz F, Taha M, Khan A, Perveen S, Choudhary MI, et al.

Eur J Med Chem, 2014 Mar 3;74:314-23.
PMID: 24486414 DOI: 10.1016/j.ejmech.2014.01.001

Thiourea derivatives (1-38) were synthesized and evaluated for their urease inhibition potential. The synthetic compounds showed a varying degree of in vitro urease inhibition with IC50 values 5.53 ± 0.02-91.50 ± 0.08 μM, most of which are superior to the standard thiourea (IC₅₀ = 21.00 ± 0.11 μM). In order to ensure the mode of inhibition of these compounds, the kinetic study of the most active compounds has been carried out. Most of these inhibitors were found to be mixed-type of inhibitors, except compounds 13 and 30 which were competitive, while compound 19 was identified as non-competitive inhibitor with Ki values between 8.6 and 19.29 μM.

Matched MeSH terms: Urease/antagonists & inhibitors*
Antagonizing IL-6 in ankylosing spondylitis: a short review

Rajalingham S, Das S

Inflamm Allergy Drug Targets, 2012 Aug 1;11(4):262-5.
PMID: 22452603

Ankylosing spondylitis (AS) is a chronic inflammatory disorder with predilection for the axial skeleton, leading to progressive restricted mobility and deformity of the spine. The fundamental mechanism involves autoimmunity orchestrated by T cells. Similar to other rheumatic diseases, the complex interplay of cytokines such as tumour necrosis factor alpha, interleukin-6 (IL 6) and interleukin-10 (IL 10) has been implicated in the pathogenesis of the disease. Despite extensive research over the past decades, the treatment options for AS, are limited. Non steroidal antiinflammatory drugs are the first line of therapy, whereas anti TNF drugs are administered for refractory cases which fail to respond to the treatment. There have been conflicting views on the correlation of IL 6 with disease activity in AS. As such, the debate on the role of anti IL6 in AS is still ongoing. Anti IL 6 such as tocilizumab and siltuximab have proven efficacy based on the large randomized controlled trials. The Food and Drug Administration (FDA) has approved these drugs for treating rheumatoid arthritis and systemic juvenile idiopathic arthritis. Researchers have adventurously experimented anti IL 6 therapy in AS but the conclusions made were not consolidated into international guidelines or consensus statement for clinical practice. In the present review, we explore the role of anti IL6 in the treatment of AS based on the cumulative evidence over recent years.

Matched MeSH terms: Interleukin-6/antagonists & inhibitors*
Review on pharmacological activities of Cinnamomum subavenium

Lee CH, Kuo CN, Chen HL, Chen CY

Nat Prod Res, 2013;27(11):988-91.
PMID: 22691063 DOI: 10.1080/14786419.2012.695369

This review describes the morphological, phytochemical and pharmacological properties of Cinnamomum subavenium (Lauraceae). The plant grows wild in southern Mainland China, Burma, Cambodia, Taiwan, Malaysia and Indonesia. This plant is recorded as having long been used to treat carcinomatous swelling, stomach ache, chest pain, abdominal pain, hernia, diarrhoea, rheumatism, nausea and vomiting. This article enumerates an overview of phytochemical and pharmacological aspects that is useful to researchers for further exploration for the necessary development of this potential herb.

Matched MeSH terms: Monophenol Monooxygenase/antagonists & inhibitors
Thermodynamics and inhibition studies of lipozyme TL IM in biodiesel production via enzymatic transesterification

Khor GK, Sim JH, Kamaruddin AH, Uzir MH

Bioresour Technol, 2010 Aug;101(16):6558-61.
PMID: 20363621 DOI: 10.1016/j.biortech.2010.03.047

In order to characterize enzyme activity and stability corresponding to temperature effects, thermodynamic studies on commercial immobilized lipase have been carried out via enzymatic transesterification. An optimum temperature of 40 degrees C was obtained in the reaction. The decreasing reaction rates beyond the optimum temperature indicated the occurrence of reversible enzyme deactivation. Thermodynamic studies on lipase denaturation exhibited a first-order kinetics pattern, with considerable stability through time shown by the lipase as well. The activation and deactivation energies were 22.15 kJ mol(-1) and 45.18 kJ mol(-1), respectively, implying more energy was required for the irreversible denaturation of the enzyme to occur. At water content of 0.42%, the initial reaction rate and FAME yield displayed optimum values of 3.317 g/L min and 98%, respectively.

Matched MeSH terms: Lipase/antagonists & inhibitors
Fulltext Phosphorylation of Human Choline Kinase Beta by Protein Kinase A: Its Impact on Activity and Inhibition

Chang CC, Few LL, Konrad M, See Too WC

PLoS One, 2016;11(5):e0154702.
PMID: 27149373 DOI: 10.1371/journal.pone.0154702

Choline kinase beta (CKβ) is one of the CK isozymes involved in the biosynthesis of phosphatidylcholine. CKβ is important for normal mitochondrial function and muscle development as the lack of the ckβ gene in human and mice results in the development of muscular dystrophy. In contrast, CKα is implicated in tumorigenesis and has been extensively studied as an anticancer target. Phosphorylation of human CKα was found to regulate the enzyme's activity and its subcellular location. This study provides evidence for CKβ phosphorylation by protein kinase A (PKA). In vitro phosphorylation of CKβ by PKA was first detected by phosphoprotein staining, as well as by in-gel kinase assays. The phosphorylating kinase was identified as PKA by Western blotting. CKβ phosphorylation by MCF-7 cell lysate was inhibited by a PKA-specific inhibitor peptide, and the intracellular phosphorylation of CKβ was shown to be regulated by the level of cyclic adenosine monophosphate (cAMP), a PKA activator. Phosphorylation sites were located on CKβ residues serine-39 and serine-40 as determined by mass spectrometry and site-directed mutagenesis. Phosphorylation increased the catalytic efficiencies for the substrates choline and ATP about 2-fold, without affecting ethanolamine phosphorylation, and the S39D/S40D CKβ phosphorylation mimic behaved kinetically very similar. Remarkably, phosphorylation drastically increased the sensitivity of CKβ to hemicholinium-3 (HC-3) inhibition by about 30-fold. These findings suggest that CKβ, in concert with CKα, and depending on its phosphorylation status, might play a critical role as a druggable target in carcinogenesis.

Matched MeSH terms: Choline Kinase/antagonists & inhibitors
Design and synthesis of new barbituric- and thiobarbituric acid derivatives as potent urease inhibitors: Structure activity relationship and molecular modeling studies

Rauf A, Shahzad S, Bajda M, Yar M, Ahmed F, Hussain N, et al.

Bioorg Med Chem, 2015 Sep 1;23(17):6049-58.
PMID: 26081763 DOI: 10.1016/j.bmc.2015.05.038

In this study 36 new compounds were synthesized by condensing barbituric acid or thiobarbituric acid and respective anilines (bearing different substituents) in the presence of triethyl orthoformate in good yields. In vitro urease inhibition studies against jack bean urease revealed that barbituric acid derived compounds (1-9 and 19-27) were found to exhibit low to moderate activity however thiobarbituric acid derived compounds (10-18 and 28-36) showed significant inhibition activity at low micro-molar concentrations. Among the synthesized compounds, compounds (15), (12), (10), (36), (16) and (35) showed excellent urease inhibition with IC50 values 8.53 ± 0.027, 8.93 ± 0.027, 12.96 ± 0.13, 15 ± 0.098, 18.9 ± 0.027 and 19.7 ± 0.63 μM, respectively, even better than the reference compound thiourea (IC50 = 21 ± 0.011). The compound (11) exhibited comparable activity to the standard with IC50 value 21.83 ± 0.19 μM. In silico molecular docking studies for most active compounds (10), (12), (15), (16), (35) and (36) and two inactive compounds (3) and (6) were performed to predict the binding patterns.

Matched MeSH terms: Urease/antagonists & inhibitors*
Inactivation of insecticides by bacteria isolated from polluted waters where the mosquito larva bred in large number

Hirakoso S, Kitago I, Harinasuta C

Med J Malaya, 1968 Mar;22(3):249.
PMID: 4386490
Matched MeSH terms: Insecticides/antagonists & inhibitors*
Fulltext Galactose as novel target against Acanthamoeba cysts

Anwar A, Khan NA, Siddiqui R

PLoS Negl Trop Dis, 2019 07;13(7):e0007385.
PMID: 31348789 DOI: 10.1371/journal.pntd.0007385
Matched MeSH terms: Galactose/antagonists & inhibitors*
Synthesis, α-glycosidase inhibitory potential and molecular docking study of benzimidazole derivatives

Taha M, Rahim F, Zaman K, Selvaraj M, Uddin N, Farooq RK, et al.

Bioorg Chem, 2020 01;95:103555.
PMID: 31911306 DOI: 10.1016/j.bioorg.2019.103555

A series of twenty-six analogs of benzimidazole based oxadiazole have been synthesized and evaluated against alpha-glycosidase enzyme. Most the analogs showed excellent to good inhibitory potential. Among the screened analogs, analog 1, 2, 3 and 14 with IC50 values 4.6 ± 0.1, 9.50 ± 0.3, 2.6 ± 0.1 and 9.30 ± 0.4 µM respectively showedexcellent inhibitory potential than reference drug acarbose (IC50 = 38.45 ± 0.80 µM). Some of the analogs like 19, 21, 22 and 23 with methyl and methoxy substituent on phenyl ring show hydrophobic interaction and were found with no inhibitory potential. The binding interactions between synthesized analogs and ligands protein were confirmed through molecular docking study. Various spectroscopic techniques like 1H NMR, 13C NMR, and EI-MS were used for characterization of all synthesized analogs. These derivatives were synthesized by simple mode of synthesis like heterocyclic ring formation.

Matched MeSH terms: Glycoside Hydrolases/antagonists & inhibitors*
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.

Matched MeSH terms: alpha-Amylases/antagonists & inhibitors*
Interleukin 23 and autoimmune diseases: current and possible future therapies

Abdo AIK, Tye GJ

Inflamm Res, 2020 May;69(5):463-480.
PMID: 32215665 DOI: 10.1007/s00011-020-01339-9

PURPOSE: IL-23 is a central proinflammatory cytokine with a wide range of influence over immune response. It is implicated in several autoimmune diseases due to the infinite inflammatory loops it can create through the positive feedbacks of both IL-17 and IL-22 arms. This made IL-23 a key target of autoimmune disorders therapy, which indeed was proven to inhibit inflammation and ameliorate diseases. Current autoimmune treatments targeting IL-23 are either by preventing IL-23 ligation to its receptor (IL-23R) via antibodies or inhibiting IL-23 signaling by signaling downstream mediators' inhibitors, with each approach having its own pros and cons.
METHODS: Literature review was done to further understand the biology of IL-23 and current therapies.
RESULTS: In this review, we discuss the biological features of IL-23 and its role in the pathogenesis of autoimmune diseases including psoriasis, rheumatoid arthritis and inflammatory bowel diseases. Advantages, limitations and side effects of each concept will be reviewed, suggesting several advanced IL-23-based bio-techniques to generate new and possible future therapies to overcome current treatments problems.

Matched MeSH terms: Interleukin-23/antagonists & inhibitors

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