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The relevance of polymeric synthetic membranes in topical formulation assessment and drug diffusion study

Ng SF, Rouse JJ, Sanderson FD, Eccleston GM

Arch Pharm Res, 2012 Mar;35(4):579-93.
PMID: 22553050 DOI: 10.1007/s12272-012-0401-7

Synthetic membranes are composed of thin sheets of polymeric macromolecules that can control the passage of components through them. Generally, synthetic membranes used in drug diffusion studies have one of two functions: skin simulation or quality control. Synthetic membranes for skin simulation, such as the silicone-based membranes polydimethylsiloxane and Carbosil, are generally hydrophobic and rate limiting, imitating the stratum corneum. In contrast, synthetic membranes for quality control, such as cellulose esters and polysulfone, are required to act as a support rather than a barrier. These synthetic membranes also often contain pores; hence, they are called porous membranes. The significance of Franz diffusion studies and synthetic membranes in quality control studies involves an understanding of the fundamentals of synthetic membranes. This article provides a general overview of synthetic membranes, including a brief background of the history and the common applications of synthetic membranes. This review then explores the types of synthetic membranes, the transport mechanisms across them, and their relevance in choosing a synthetic membrane in Franz diffusion cell studies for formulation assessment purposes.

Matched MeSH terms: Drug Evaluation, Preclinical
Anti-arthritic potential of the plant Justicia gendarussa Burm F

Paval J, Kaitheri SK, Potu BK, Govindan S, Kumar RS, Narayanan SN, et al.

Clinics (Sao Paulo), 2009;64(4):357-62.
PMID: 19488595

OBJECTIVE: To evaluate the anti-arthritic potential of the plant Justicia gendarussa using two different rat models.
MATERIALS AND METHOD: The anti-arthritic potential of the alcoholic extract of the plant Justicia gendarussa was evaluated using the Freund's adjuvant-induced and collagen-induced arthritic rat models. The rats were treated with the ethanolic extract of Justicia gendarussa and with standard aspirin.
RESULTS: The ethanolic extract of Justicia gendarussa showed significant anti-arthritic activity that was statistically similar to that of aspirin. Our results suggest that the alcoholic extract of Justicia gendarussa exhibits significant anti-arthritic potential.

Matched MeSH terms: Drug Evaluation, Preclinical
Fulltext Identification of novel human USP2 inhibitor and its putative role in treatment of COVID-19 by inhibiting SARS-CoV-2 papain-like (PLpro) protease

Mirza MU, Ahmad S, Abdullah I, Froeyen M

Comput Biol Chem, 2020 Dec;89:107376.
PMID: 32979815 DOI: 10.1016/j.compbiolchem.2020.107376

Human ubiquitin carboxyl-terminal hydrolase-2 (USP2) inhibitors, such as thiopurine analogs, have been reported to inhibit SARS-CoV papain-like proteases (PLpro). The PLpro have significant functional implications in the innate immune response during SARS-CoV-2 infection and considered an important antiviral target. Both proteases share strikingly similar USP fold with right-handed thumb-palm-fingers structural scaffold and conserved catalytic triad Cys-His-Asp/Asn. In this urgency situation of COVID-19 outbreak, there is a lack of in-vitro facilities readily available to test SARS-CoV-2 inhibitors in whole-cell assays. Therefore, we adopted an alternate route to identify potential USP2 inhibitor through integrated in-silico efforts. After an extensive virtual screening protocol, the best compounds were selected and tested. The compound Z93 showed significant IC50 value against Jurkat (9.67 μM) and MOTL-4 cells (11.8 μM). The binding mode of Z93 was extensively analyzed through molecular docking, followed by MD simulations, and molecular interactions were compared with SARS-CoV-2. The relative binding poses of Z93 fitted well in the binding site of both proteases and showed consensus π-π stacking and H-bond interactions with histidine and aspartate/asparagine residues of the catalytic triad. These results led us to speculate that compound Z93 might be the first potential chemical lead against SARS-CoV-2 PLpro, which warrants in-vitro evaluations.

Matched MeSH terms: Drug Evaluation, Preclinical
Fulltext In vitro drug susceptibility of Acanthamoeba castellani to chloroquine, ivermectin and fungizon

Rain AN, Radzan T, Sajiri S, Mak JW

Southeast Asian J Trop Med Public Health, 1996 Jun;27(2):319-24.
PMID: 9279996

In vitro sensitivity of Acanthamoeba castellani was tested to three drugs: Chloroquine, ivermectin and fungizone (amphotericin B). Sensitivity was demonstrated to the latter two compounds but not to chloroquine. Thus ivermectin and amphotericin B show promise as therapeutic agents against this parasite.

Matched MeSH terms: Drug Evaluation, Preclinical
Caffeic acid phenethyl ester (CAPE): scavenger of peroxynitrite in vitro and in sepsis models

Kassim M, Mansor M, Kamalden TA, Shariffuddin II, Hasan MS, Ong G, et al.

Shock, 2014 Aug;42(2):154-60.
PMID: 24667629 DOI: 10.1097/SHK.0000000000000179

Excessive free radical production by immune cells has been linked to cell death and tissue injury during sepsis. Peroxynitrite is a short-lived oxidant and a potent inducer of cell death that has been identified in several pathological conditions. Caffeic acid phenethyl ester (CAPE) is an active component of honeybee products and exhibits antioxidant, anti-inflammatory, and immunomodulatory activities. The present study examined the ability of CAPE to scavenge peroxynitrite in RAW 264.7 murine macrophages stimulated with lipopolysaccharide/interferon-γ that was used as an in vitro model. Conversion of 123-dihydrorhodamine to its oxidation product 123-rhodamine was used to measure peroxynitrite production. Two mouse models of sepsis (endotoxemia and cecal ligation and puncture) were used as in vivo models. The level of serum 3-nitrotyrosine was used as an in vivo marker of peroxynitrite. The results demonstrated that CAPE significantly improved the viability of lipopolysaccharide/interferon-γ-treated RAW 264.7 cells and significantly inhibited nitric oxide production, with effects similar to those observed with an inhibitor of inducible nitric oxide synthase (1400W). In addition, CAPE exclusively inhibited the synthesis of peroxynitrite from the artificial substrate SIN-1 and directly prevented the peroxynitrite-mediated conversion of dihydrorhodamine-123 to its fluorescent oxidation product rhodamine-123. In both sepsis models, CAPE inhibited cellular peroxynitrite synthesis, as evidenced by the absence of serum 3-nitrotyrosine, an in vivo marker of peroxynitrite. Thus, CAPE attenuates the inflammatory responses that lead to cell damage and, potentially, cell death through suppression of the production of cytotoxic molecules such as nitric oxide and peroxynitrite. These observations provide evidence of the therapeutic potential of CAPE treatment for a wide range of inflammatory disorders.

Matched MeSH terms: Drug Evaluation, Preclinical/methods
Fulltext Discovery of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model

Kong C, Yehye WA, Abd Rahman N, Tan MW, Nathan S

BMC Complement Altern Med, 2014;14:4.
PMID: 24393217 DOI: 10.1186/1472-6882-14-4

The limited antibiotic options for effective control of methicillin-resistant Staphylococcus aureus infections has led to calls for new therapeutic approaches to combat this human pathogen. An alternative approach to control MRSA is through the use of anti-infective agents that selectively disrupt virulence-mediated pathways without affecting microbial cell viability or by modulating the host natural immune defenses to combat the pathogen.

Matched MeSH terms: Drug Evaluation, Preclinical/methods*
In vitro and in vivo anti-inflammatory activities of columbin through the inhibition of cycloxygenase-2 and nitric oxide but not the suppression of NF-κB translocation

Ibrahim Abdelwahab S, Syaed Koko W, Mohamed Elhassan Taha M, Mohan S, Achoui M, Ameen Abdulla M, et al.

Eur J Pharmacol, 2012 Mar 5;678(1-3):61-70.
PMID: 22227329 DOI: 10.1016/j.ejphar.2011.12.024

Columbin, a diterpenoid furanolactone, was isolated purely for the first time from the plant species Tinspora bakis. The anti-inflammatory effects of columbin were studied in vitro, in silico and in vivo. The effect of columbin on nitric oxide was examined on lipopolysaccharide-interferon-gamma (LPS/IFN) induced RAW264.7 macrophages. In vitro and in silico cyclooxygenase-1 and cyclooxygenase-2 inhibitory activities of columbin using biochemical kit and molecular docking, respectively, were investigated. Mechanism of columbin in suppressing NF-kappaB-translocation was tested using Cellomics®NF-κB activation assay and ArrayScan Reader in LPS-stimulated RAW264.7 cells. Moreover, effects of columbin in vivo that were done on carrageenan-induced mice paw-oedema were tested. Lastly, the in vitro and in vivo toxicities of columbin were examined on human liver cells and mice, respectively. Treatment with columbin or N(ω)-nitro-l-arginine methyl ester (l-NAME) inhibited LPS/IFN-γ-induced NO production without affecting the viability of RAW264.7. Pre-treatment of stimulated cells with columbin did not inhibit the translocation of NF-κB to the nucleus in LPS-stimulated cells. COX-1 and COX-2 inhibitory activities of columbin were 63.7±6.4% and 18.8±1.5% inhibition at 100μM, respectively. Molecular docking study further helped in supporting the observed COX-2 selectivity. Whereby, the interaction of columbin with Tyr385 and Arg120 signifies its higher activity in COX-2, as Tyr385 was reported to be involved in the abstraction of hydrogen from C-13 of arachidonate, and Arg120 is critical for high affinity arachidonate binding. Additionally, columbin inhibited oedema formation in mice paw. Lastly, the compound was observed to be safe in vitro and in vivo. This study presents columbin as a potential anti-inflammatory drug.

Matched MeSH terms: Drug Evaluation, Preclinical/methods
The effect of Malaysian cocoa extract on glucose levels and lipid profiles in diabetic rats

Ruzaidi A, Amin I, Nawalyah AG, Hamid M, Faizul HA

J Ethnopharmacol, 2005 Apr 8;98(1-2):55-60.
PMID: 15763363

The present study aims to investigate the effect of cocoa extract on serum glucose levels and lipid profiles in streptozotocin-diabetic rats. Cocoa extract (contained 285.6 mg total polyphenol per gram extract) was prepared from fermented and roasted (140 degrees C, 20 min) beans by extracting using 80% ethanol in the ratio of 1-10. The extract of three dosages (1, 2, and 3%) was fed to normal and diabetic rats for a period of 4 weeks. In hyperglycaemic group, cocoa extract (1 and 3%) diets were found to significantly lower (p<0.05) the serum glucose levels compared to the control. Furthermore, supplementation of 1 and 3% cocoa extract had significantly reduced (p<0.05) the level of total cholesterol in diabetic rats. In addition, 1, 2, and 3% cocoa extract diets had significantly lowered (p<0.05) the total triglycerides. Interestingly, this study found that serum HDL-cholesterol had increased significantly (p<0.05) in diabetic rats fed with 2% cocoa extract, while the LDL-cholesterol had decreased significantly (p<0.05) in the 1% treated group. These results indicate that cocoa extract may possess potential hypoglycaemic and hypocholestrolemic effects on serum glucose levels and lipid profiles, respectively. The results also found that the effect of cocoa extract was dose-dependent.

Matched MeSH terms: Drug Evaluation, Preclinical/methods
Biologically active vallesamine, strychnan, and rhazinilam alkaloids from Alstonia: Pneumatophorine, a nor-secovallesamine with unusual incorporation of a 3-ethylpyridine moiety

Lim JL, Sim KS, Yong KT, Loong BJ, Ting KN, Lim SH, et al.

Phytochemistry, 2015 Sep;117:317-24.
PMID: 26125941 DOI: 10.1016/j.phytochem.2015.06.024

Four alkaloids comprising two vallesamine, one strychnan, and one pyranopyridine alkaloid, in addition to 32 other known alkaloids were isolated from two Malayan Alstonia species, Alstonia pneumatophora and Alstonia rostrata. The structures of these alkaloids were determined using NMR and MS analyses, and in one instance, confirmed by X-ray diffraction analysis. The nor-6,7-secovallesamine alkaloid, pneumatophorine, is notable for an unusual incorporation of a 3-ethylpyridine moiety in a monoterpenoid indole. The rhazinilam-type alkaloids (rhazinicine, nor-rhazinicine, rhazinal, and rhazinilam) showed strong cytotoxicity toward human KB, HCT-116, MDA-MB-231, and MRC-5 cells, while pneumatophorine, the uleine alkaloid undulifoline, and the strychnan alkaloids, N4-demethylalstogustine and echitamidine, induced concentration dependent relaxation in phenylephrine-precontracted rat aortic rings.

Matched MeSH terms: Drug Evaluation, Preclinical/methods
Safety against nephrotoxicity in paclitaxel treatment: Oral nanocarrier as an effective tool in preclinical evaluation with marked in vivo antitumor activity

Choudhury H, Gorain B, Tekade RK, Pandey M, Karmakar S, Pal TK

Regul Toxicol Pharmacol, 2017 Dec;91:179-189.
PMID: 29080846 DOI: 10.1016/j.yrtph.2017.10.023

Oral paclitaxel (PTXL) formulations freed from cremophor® EL (CrEL) is always in utmost demand by the cancerous patients due to toxicities associated with the currently marketed formulation. In our previous investigation [Int. J. Pharm. 2014; 460:131], we have developed an oral oil based nanocarrier for the lipophilic drug, PTXL to target bioavailability issue and patient compliance. Here, we report in vivo antitumor activity and 28-day sub-chronic toxicity of the developed PTXL nanoemulsion. It was observed that the apoptotic potential of oral PTXL nanoemulsion significantly inhibited the growth of solid tumor (59.2 ± 7.17%; p

Matched MeSH terms: Drug Evaluation, Preclinical/methods
Phytochemical profile of Orthosiphon aristatus extracts after storage: Rosmarinic acid and other caffeic acid derivatives

Chua LS, Lau CH, Chew CY, Ismail NIM, Soontorngun N

Phytomedicine, 2018 Jan 15;39:49-55.
PMID: 29433683 DOI: 10.1016/j.phymed.2017.12.015

BACKGROUND: Orthosiphon aristatus (Blume) Miq. is a medicinal herb which is traditionally used for the treatment of diabetes and kidney diseases in South East Asia. Previous studies reported higher concentration of antioxidative phytochemicals, especially rosmarinic acid (ester of caffeic acid) and other caffeic acid derivatives in this plant extract than the other herbs such as rosemary and sage which are usually used as raw materials to produce rosmarinic acid supplement in the market.
PURPOSE: The phytochemical profile of O. aristatus was investigated at different storage durations for quality comparison.
METHODS: The phytochemicals were extracted from the leaves and stems of O. aristatus using a reflux reactor. The extracts were examined for total phenolic and flavonoid contents, as well as their antioxidant capacities, in terms of radical scavenging, metal chelating and reducing power. The phytochemical profiles were also analyzed by unsupervised principal component analysis and hierarchical cluster analysis, in relation to the factor of storage at 4 °C for 5 weeks.
RESULTS: The leaf extract was likely to have more phytochemicals than stem extract, particularly caffeic acid derivatives including glycosylated and alkylated caffeic acids. This explains higher ratio of total phenolic content to total flavonoid content with higher antioxidant capacities for the leaf extracts. Rosmarinic acid dimer and salvianolic acid B appeared to be the major constituents, possibly contributing to the previously reported pharmacological properties. However, the phytochemical profiles were found changing, even though the extracts were stored in the refrigerator (4 °C). The change was significantly observed at the fifth week based on the statistical pattern recognition technique.
CONCLUSION: O. aristatus could be a promising source of rosmarinic acid and its dimer, as well as salvianolic acid B with remarkably antioxidant properties. The phytochemical profile was at least stable for a month stored at 4 °C. It is likely to be a good choice of herbal tea with comparable radical scavenging activity, but lower caffeine content than other tea samples.

Matched MeSH terms: Drug Evaluation, Preclinical/methods
Fulltext Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses

Zandi K, Bassit L, Amblard F, Cox BD, Hassandarvish P, Moghaddam E, et al.

Antimicrob Agents Chemother, 2019 Jul;63(7).
PMID: 31061163 DOI: 10.1128/AAC.00397-19

Dengue virus (DENV) and Japanese encephalitis virus (JEV) are important arthropod-borne viruses from the Flaviviridae family. DENV is a global public health problem with significant social and economic impacts, especially in tropical and subtropical areas. JEV is a neurotropic arbovirus endemic to east and southeast Asia. There are no U.S. FDA-approved antiviral drugs available to treat or to prevent DENV and JEV infections, leaving nearly one-third of the world's population at risk for infection. Therefore, it is crucial to discover potent antiviral agents against these viruses. Nucleoside analogs, as a class, are widely used for the treatment of viral infections. In this study, we discovered nucleoside analogs that possess potent and selective anti-JEV and anti-DENV activities across all serotypes in cell-based assay systems. Both viruses were susceptible to sugar-substituted 2'-C-methyl analogs with either cytosine or 7-deaza-7-fluoro-adenine nucleobases. Mouse studies confirmed the anti-DENV activity of these nucleoside analogs. Molecular models were assembled for DENV serotype 2 (DENV-2) and JEV RNA-dependent RNA polymerase replication complexes bound to nucleotide inhibitors. These models show similarities between JEV and DENV-2, which recognize the same nucleotide inhibitors. Collectively, our findings provide promising compounds and a structural rationale for the development of direct-acting antiviral agents with dual activity against JEV and DENV infections.

Matched MeSH terms: Drug Evaluation, Preclinical/methods
Fulltext In vitro and ex-vivo cellular antioxidant protection and cognitive enhancing effects of an extract of Polygonum minus Huds (Lineminus™) demonstrated in a Barnes Maze animal model for memory and learning

George A, Ng CP, O'Callaghan M, Jensen GS, Wong HJ

BMC Complement Altern Med, 2014;14:161.
PMID: 24886679 DOI: 10.1186/1472-6882-14-161

Polygonum minus Huds.is a culinary flavouring that is common in South East Asian cuisine and as a remedy for diverse maladies ranging from indigestion to poor eyesight. The leaves of this herb have been reported to be high in antioxidants. Flavonoids which have been associated with memory, cognition and protection against neurodegeneration were found in P. minus.

Matched MeSH terms: Drug Evaluation, Preclinical
Fulltext In vitro evaluation of Pandanus amaryllifolius ethanol extract for induction of cell death on non-hormone dependent human breast adenocarcinoma MDA-MB-231 cell via apoptosis

Chong HZ, Yeap SK, Rahmat A, Akim AM, Alitheen NB, Othman F, et al.

BMC Complement Altern Med, 2012;12:134.
PMID: 22909149 DOI: 10.1186/1472-6882-12-134

Our previous study had shown that P. amaryllifolius was able to selectively inhibit cell proliferation of hormone independent breast cancer cell line MDA-MB-231. To understand the mode of killing and mechanism of action for P. amaryllifolius, the ethanol extract was evaluated for their alteration of cell cycle progression, PS externalization, DNA fragmentation and expression of anti/pro-apoptotic related protein.

Matched MeSH terms: Drug Evaluation, Preclinical
Immunomodulatory effects of zerumbone isolated from roots of Zingiber zerumbet

Keong YS, Alitheen NB, Mustafa S, Abdul Aziz S, Abdul Rahman M, Ali AM

Pak J Pharm Sci, 2010 Jan;23(1):75-82.
PMID: 20067871

In this study, the immunomodulatory effects of zerumbone isolated from Zingiber zerumbet were investigated by evaluating the effects of this compound towards the lymphocytes proliferation (mice thymocytes, mice splenocytes and human human peripheral blood mononuclear cells, PBMC), cell cycle progression and cytokine (interleukin 2 and 12) induction. Lymphocyte proliferation assay showed that zerumbone was able to activate mice thymocytes, splenocytes and PBMC at dosage dependent pattern where the best concentration was 7.5 microg/ml. Flow cytometry analysis showed the highest population of PBMC entered into G2/M phase after treatment for 72 h with 7.5 microg/ml zerumbone. The production of human interleukin-2 and human interleukin-12 cytokines in culture supernatant from zerumbone activated lymphocytes was prominently upregulated at 24 hour and decreased from 48 h to 72 h. The above results indicate that zerumbone can be used as immunomodulatory agent which can react toward the immune cell cytokine production in dosage dependent pattern.

Matched MeSH terms: Drug Evaluation, Preclinical
Safety and efficacy of rapid dose administration of quetiapine in bipolar mania

Hatim A, Habil H, Jesjeet SG, Low CC, Joseph J, Jambunathan ST, et al.

Hum Psychopharmacol, 2006 Jul;21(5):313-8.
PMID: 16856220

In this open-label pilot study, 20 adult patients hospitalized for acute bipolar mania received oral quetiapine as a single evening dose of 200 mg on day 1, increased by 200 mg/day on days 2, 3, and 4 until 800 mg/day taken in 2 divided doses on day 4. From day 5 onward, patients received a flexible total dose of 400-800 mg/day until completion of 3 weeks of treatment. Safety and tolerability were assessed by adverse-event (AE)-related dropouts in week 1, incidence of AEs including EPS, changes in electrocardiogram, and vital signs. Efficacy was assessed using the YMRS, PANSS, and CGI scales. Nineteen of 20 patients (95%) completed the quetiapine rapid titration during week 1. Significant improvement was observed in YMRS, PANSS, and CGI Severity of Illness scores by day 5, and was maintained throughout the study. A reduction of > or = 50% in YMRS score was achieved by 75% of patients by day 7, and maintained to day 21. Overall, 20% of patients discontinued due to AEs. Agitation was the most common cause of AE-related study discontinuation. Thirty-five per cent of patients required dose adjustment due to AEs after rapid dose administration was completed. Most patients tolerated rapid titration of quetiapine to 800 mg/day by day 4 of therapy, with a significant improvement in manic symptoms by day 7 of treatment.

Matched MeSH terms: Drug Evaluation
Mutagenicity and preclinical safety assessment of the aqueous extract of Clinacanthus nutans leaves

Farsi E, Esmailli K, Shafaei A, Moradi Khaniabadi P, Al Hindi B, Khadeer Ahamed MB, et al.

Drug Chem Toxicol, 2016 Oct;39(4):461-73.
PMID: 27033971 DOI: 10.3109/01480545.2016.1157810

CONTEXT: Clinacanthus nutans (CN) is used traditionally for treating various illnesses. Robust safety data to support its use is lacking.
OBJECTIVE: To evaluate the adverse effects of aqueous extract of CN leaves (AECNL).
MATERIALS AND METHODS: The oral toxicity of the AECNL was tested following Organisation for Economic Co-operation and Development (OECD) guidelines. Mutagenicity (Ames test) of AECNL was evaluated using TA98 and TA100 Salmonella typhimurium strains.
RESULTS: No mortality or morbidity was found in the animals upon single and repeated dose administration. However, significant body weight loss was observed at 2000 mg/kg during sub-chronic (90 d) exposure. In addition, increased eosinophil at 500 mg/kg and decreased serum alkaline phosphatase levels at 2000 mg/kg were observed in male rats. Variations in glucose and lipid profiles in treated groups were also observed compared to control. Ames test revealed no evidence of mutagenic or carcinogenic effects at 500 μg/well of AECNL.
CONCLUSION: The median lethal dose (LD50) of the AECNL is >5000 mg/kg and the no-observed-adverse-effect level is identified to be greater than 2000 mg/kg/day in 90-d study.

Matched MeSH terms: Drug Evaluation, Preclinical
Comparative study of DDT, carbaryl (Sevin) and Actellic (pirimiphos-methyl) in the treatment of Pediculus humanus capitis infestation

Sinniah B, Sinniah D

Public Health, 1983 Jan;97(1):3-7.
PMID: 6405446
Matched MeSH terms: Drug Evaluation
Effect of melatonin supplementation and cross-fostering on renal glutathione system and development of hypertension in spontaneously hypertensive rats

Siew-Keah L, Sundaram A, Sirajudeen KN, Zakaria R, Singh HJ

J Physiol Biochem, 2014 Mar;70(1):73-9.
PMID: 23975651 DOI: 10.1007/s13105-013-0282-3

Antenatal and postnatal environments are hypothesised to influence the development of hypertension. This study investigates the synergistic effect of cross-fostering and melatonin supplementation on the development of hypertension and renal glutathione system in spontaneously hypertensive rats (SHR). In one experiment, 1-day-old male SHR pups were fostered to either SHR (shr-SHR) or Wistar-Kyoto rats, (shr-WKY). In a concurrent experiment, SHR dams were given melatonin in drinking water (10 mg/kg body weight) from day 1 of pregnancy. Immediately following delivery, 1-day-old male pups were fostered either to SHR (Mel-shr-SHR) or WKY (Mel-shr-WKY) dams receiving melatonin supplementation until weaning on day 21. Upon weaning, melatonin supplementation was continued to these pups until the age of 16 weeks. Systolic blood pressures (SBP) were recorded at the age of 4, 6, 8, 12 and 16 weeks. Renal antioxidant activities were measured. Mean SBP of shr-WKY, Mel-shr-SHR and Mel-shr-WKY was significantly lower than that in shr-SHR until the age of 8 weeks. At 12 and 16 weeks of age, mean SBP of Mel-shr-WKY was lower than those in non-treated shr-SHR and shr-WKY pups but was not significantly different from that in Mel-shr-SHR. Renal glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities were significantly higher in Mel-shr-SHR and Mel-shr-WKY at 16 weeks of age. It appears that combination of cross-fostering and melatonin supplementation exerts no synergistic effect on delaying the rise in blood pressure in SHR. The elevated GPx and GST activities are likely to be due to the effect of melatonin supplementation.

Matched MeSH terms: Drug Evaluation, Preclinical
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.

Matched MeSH terms: Drug Evaluation, Preclinical

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