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1,3,5-Triazine-based analogues of purine: from isosteres to privileged scaffolds in medicinal chemistry

Lim FP, Dolzhenko AV

Eur J Med Chem, 2014 Oct 6;85:371-90.
PMID: 25105925 DOI: 10.1016/j.ejmech.2014.07.112

Purines can be considered as the most ubiquitous and functional N-heterocyclic compounds in nature. Structural modifications of natural purines, particularly using isosteric ring systems, have been in the focus of many drug discovery programs. Fusion of 1,3,5-triazine ring with pyrrole, pyrazole, imidazole, 1,2,3-triazole or 1,2,4-triazole results in seven bicyclic heterocyclic systems isosteric to purine. Application of the isosterism concept for the development of new compounds with therapeutic potential in areas involving purinergic regulation or purine metabolism led to significant advances in medicinal chemistry of the azolo[1,3,5]triazines. These 1,3,5-triazine-based purine-like scaffolds significantly increase level of molecular diversity and allow covering chemical space in the important areas of medicinal chemistry. Some of these azolo[1,3,5]triazine systems have become privileged scaffolds in the development of inhibitors of various kinases, phosphodiesterase, xanthine oxidase, and thymidine phosphorylase, antagonists of adenosine and corticotropin-releasing hormone receptors, anticancer and antiviral agents.

Matched MeSH terms: Enzyme Inhibitors/metabolism; Enzyme Inhibitors/pharmacology; Enzyme Inhibitors/chemistry*
2'-Aryl and 4'-arylidene substituted pyrazolones: As potential α-amylase inhibitors

Yousuf S, Khan KM, Salar U, Chigurupati S, Muhammad MT, Wadood A, et al.

Eur J Med Chem, 2018 Nov 05;159:47-58.
PMID: 30268823 DOI: 10.1016/j.ejmech.2018.09.052

Acarbose and voglibose are well-known α-amylase inhibitors used for the management of type-II diabetes mellitus. Unfortunately, these well-known and clinically used inhibitors are also associated with several adverse effects. Therefore, there is still need to develop the safer therapy. Despite of a broad spectrum of biological significances of pyrazolone, it is infrequently evaluated for α-amylase inhibition. Current study deals with the synthesis and biological screening of aryl and arylidene substituted pyrazolones 1-18 for their potential α-amylase inhibitory activity. Structures of synthetic derivatives 1-18 were identified by different spectroscopic techniques. All compounds 1-18 (IC50 = 1.61 ± 0.16 μM to 2.38 ± 0.09 μM) exhibited significant to moderate inhibitory potential when compared to standard acarbose (IC50 = 1.46 ± 0.26 μM). A number of derivatives including 8-12 (IC50 = 1.68 ± 0.1 μM to 1.97 ± 0.07 μM) and 14-16 (IC50 = 1.61 ± 0.16 μM to 1.93 ± 0.07 μM) were found to be significantly active. Limited SAR suggested that different substitutions on compounds do not have any significant effect on the inhibitory potential. Compounds were found to be mixed-type inhibitors revealed by kinetic studies. However, in silico study was identified a number of key features participating in the interaction with the binding site of α-amylase enzyme.

Matched MeSH terms: Enzyme Inhibitors/chemical synthesis; Enzyme Inhibitors/pharmacology*; Enzyme Inhibitors/chemistry
2-Aminothiazole-Oxadiazole Bearing N-Arylated Butanamides: Convergent Synthesis, Tyrosinase Inhibition, Kinetics, Structure-Activity Relationship, and Binding Conformations

Raza H, Rehman Sadiq Butt A, Athar Abbasi M, Aziz-Ur-Rehman, Zahra Siddiqui S, Hassan M, et al.

Chem Biodivers, 2023 Feb;20(2):e202201019.
PMID: 36597268 DOI: 10.1002/cbdv.202201019

A multi-step synthesis of novel bi-heterocyclic N-arylated butanamides was consummated through a convergent strategy and the structures of these medicinal scaffolds, 7a-h, were corroborated using spectral techniques. The in vitro analysis of these hybrid molecules revealed their potent tyrosinase inhibition as compared to the standard used. The kinetics mechanism was investigated through Lineweaver-Burk plots which exposed that, 7f, inhibited tyrosinase enzyme non-competitively by forming the enzyme-inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 0.025 μM. Their binding conformations were ascertained by in silico computational studies whereby these molecules disclosed good binding energy values (kcal/mol). So, it was anticipated from the current research that these bi-heterocyclic butanamides might be probed as imperative therapeutic agents for melanogenesis.

Matched MeSH terms: Enzyme Inhibitors/chemistry
5-Bromo-2-aryl benzimidazole derivatives as non-cytotoxic potential dual inhibitors of α-glucosidase and urease enzymes

Arshad T, Khan KM, Rasool N, Salar U, Hussain S, Asghar H, et al.

Bioorg Chem, 2017 06;72:21-31.
PMID: 28346872 DOI: 10.1016/j.bioorg.2017.03.007

On the basis of previous report on promising α-glucosidase inhibitory activity of 5-bromo-2-aryl benzimidazole derivatives, these derivatives were further screened for urease inhibitory and cytotoxicity activity in order to get more potent and non-cytotoxic potential dual inhibitor for the patients suffering from diabetes as well as peptic ulcer. In this study, all compounds showed varying degree of potency in the range of (IC50=8.15±0.03-354.67±0.19μM) as compared to standard thiourea (IC50=21.25±0.15μM). It is worth mentioning that derivatives 7 (IC50=12.07±0.05μM), 8 (IC50=10.57±0.12μM), 11 (IC50=13.76±0.02μM), 14 (IC50=15.70±0.12μM) and 22 (IC50=8.15±0.03μM) were found to be more potent inhibitors than standard. All compounds were also evaluated for cytotoxicity towards 3T3 mouse fibroblast cell line and found to be completely non-toxic. Previously benzimidazole 1-25 were also showed α-glucosidase inhibitory potential. In silico studies were performed on the lead molecules i.e.2, 7, 8, 11, 14, and 22, in order to rationalize the binding interaction of compounds with the active site of urease enzyme.

Matched MeSH terms: Enzyme Inhibitors/chemical synthesis; Enzyme Inhibitors/pharmacology*; Enzyme Inhibitors/chemistry
A Review of Bisindolylmethane as an Important Scaffold for Drug Discovery

Imran S, Taha M, Ismail NH

Curr Med Chem, 2015;22(38):4412-33.
PMID: 26438249

Bisindolylmethane and its derivatives are pharmacologically active and applicable in the field of pharmaceutical chemistry. Bisindolylmethanes have a variety of biological activities such as antihyperglycemic, antiinflammatory, antibacterial, anticancer, and antileishmanial activities, including enzyme inhibition activity. They play a crucial role in many diseases especially anticancer activity. Modifying their structure had proven to be useful in the search of new therapeutic agents. Extensive research carried out on bisindolylmethane and its derivatives shows that they are pharmacologically significant. The present review focuses on the pharmacological profile of bisindolylmethane derivatives. This review includes the current literature with an update of research findings as well as the perspectives that they hold for future research.

Matched MeSH terms: Enzyme Inhibitors/pharmacology; Enzyme Inhibitors/chemistry*
Fulltext A comparison of valsartan and perindopril in the treatment of essential hypertension in the Malaysian population

Bavanandan S, Morad Z, Ismail O, Chandran A, Thayaparan T, Singaraveloo M

Med J Malaysia, 2005 Jun;60(2):158-62.
PMID: 16114156 MyJurnal

This study was conducted to determine the tolerability and efficacy of valsartan (DIOVAN) compared to perindopril (COVERSYL) in Malaysian patients with mild to moderate hypertension. Two hundred and fifty adult Malaysian patients with a mean sitting diastolic blood pressure of more than 95 mmHg and less than 115 mmHg after a 14 day washout period were randomized to receive either valsartan 80 mg once daily (n=125) or perindopril 4 mg daily (n=125) for eight weeks. The primary end point for efficacy was the change in mean sitting systolic and diastolic blood pressure (SiSBP and SiDBP). The primary criteria for evaluation of tolerability was the incidence of adverse events. There were no significant differences between the two groups with respect to sex, age, weight, baseline sitting and standing systolic and diastolic blood pressure. At 0, 4 and 8 weeks the mean SiDBP in the valsartan group were 101.4, 92.8 and 91.0 mmHg respectively. The corresponding BP for the perindopril treated group was 102.6, 93.8 and 93.2 mmHg. (95% CI -1.39 to +3.27). There were no significant differences in the mean BP measurements between the valsartan and perindopril group at 0, 4 and 8 weeks. In each group there were significant differences between the BP at 4 and 8 weeks compared to baseline. A similar pattern was seen with SiSBP. At 4 weeks 28.7% of the valsartan and 25% of the perindopril group had their BP normalized (SiDBP <90 mmHg) The percentages of patients who responded (SiDBP reduction >10 mmHg but SiDBP >90 mmHg) were 21.3 in the valsartan group and 20.8 in the perindopril group. At 8 weeks, 31.1% of the valsartan group and 30.8% of the perindopril group had their BP normalized. The response rate was 27% and 22.5% for valsartan and perindopril respectively. The major adverse event was cough which occurred in 18 patients (14.4%) in the perindopril and 1 (0.8%) in the valsartan group at 4 weeks. At 8 weeks the figures were 24 (19.2%) and 2 (1.6%) respectively. The results indicate that Valsartan is safe and efficacious in the treatment of mild to moderate hypertension. It is equally efficacious to Perindopril and not associated with any major adverse event. It has a better tolerability profile with respect to dry cough.

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use*
Fulltext A virtual screening approach for identifying plants with anti H5N1 neuraminidase activity

Ikram NK, Durrant JD, Muchtaridi M, Zalaludin AS, Purwitasari N, Mohamed N, et al.

J Chem Inf Model, 2015 Feb 23;55(2):308-16.
PMID: 25555059 DOI: 10.1021/ci500405g

Recent outbreaks of highly pathogenic and occasional drug-resistant influenza strains have highlighted the need to develop novel anti-influenza therapeutics. Here, we report computational and experimental efforts to identify influenza neuraminidase inhibitors from among the 3000 natural compounds in the Malaysian-Plants Natural-Product (NADI) database. These 3000 compounds were first docked into the neuraminidase active site. The five plants with the largest number of top predicted ligands were selected for experimental evaluation. Twelve specific compounds isolated from these five plants were shown to inhibit neuraminidase, including two compounds with IC50 values less than 92 μM. Furthermore, four of the 12 isolated compounds had also been identified in the top 100 compounds from the virtual screen. Together, these results suggest an effective new approach for identifying bioactive plant species that will further the identification of new pharmacologically active compounds from diverse natural-product resources.

Matched MeSH terms: Enzyme Inhibitors/pharmacology*; Enzyme Inhibitors/chemistry
Fulltext ACE inhibitory activity of pangasius catfish (Pangasius sutchi) skin and bone gelatin hydrolysate

Mahmoodani F, Ghassem M, Babji AS, Yusop SM, Khosrokhavar R

J Food Sci Technol, 2014 Sep;51(9):1847-56.
PMID: 25190839 DOI: 10.1007/s13197-012-0742-8

Skin and bone gelatins of pangasius catfish (Pangasius sutchi) were hydrolyzed with alcalase to isolate Angiotensin Converting Enzyme (ACE) inhibitory peptides. Samples with the highest degree of hydrolysis (DH) were separated into different fractions with molecular weight cut-off (MWCO) sizes of 10, 3 and 1 kDa, respectively and assayed for ACE inhibitory activity. Skin and bone gelatins had highest DH of 64.87 and 68.48 % after 2 and 1 h incubation, respectively. Results from this study indicated that by decreasing the molecular weight of fractions, ACE inhibitory activity was increased. Therefore, F3 permeates (MWCO

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors
Acridine-based (thio)semicarbazones and hydrazones: Synthesis, in vitro urease inhibition, molecular docking and in-silico ADME evaluation

Isaac IO, Al-Rashida M, Rahman SU, Alharthy RD, Asari A, Hameed A, et al.

Bioorg Chem, 2019 02;82:6-16.
PMID: 30267972 DOI: 10.1016/j.bioorg.2018.09.032

Urease is a bacterial enzyme that is responsible for virulence of various pathogenic bacteria such as Staphylococcus aureus, Proteus mirabilis, Klebsiella pneumoniae, Ureaplasma urealyticum, Helicobacter pylori and Mycobacterium tuberculosis. Increased urease activity aids in survival and colonization of pathogenic bacteria causing several disorders especially gastric ulceration. Hence, urease inhibitors are used for treatment of such diseases. In search of new molecules with better urease inhibitory activity, herein we report a series of acridine derived (thio)semicarbazones (4a-4e, 6a-6l) that were found to be active against urease enzyme. Molecular docking studies were carried out to better comprehend the preferential mode of binding of these compounds against urease enzyme. Docking against urease from pathogenic bacterium S. pasteurii was also carried out with favorable results. In silico ADME evaluation was done to determine drug likeness of synthesized compounds.

Matched MeSH terms: Enzyme Inhibitors/chemical synthesis; Enzyme Inhibitors/pharmacokinetics; Enzyme Inhibitors/chemistry*
Acute Ischemic Stroke and Acute on Chronic Kidney Disease

Aftab RA, Khan AH, AbdulRazzaq HA, Adnan AS

JNMA J Nepal Med Assoc, 2016 12 10;54(202):85-87.
PMID: 27935930

Ischemic stroke is due to either local thrombus formation or emboli that occlude a cerebral artery, together with chronic kidney disease represent major mortality and morbidity.Here we present a case of 53 years old Malay man, admitted to a hospital in Malaysia complaining of sudden on set of weakness on right sided upper and lower limb associated with slurred speech. Patient was also suffering from uncontrolled hypertension, hyperlipidemia, chronic kidney disease stage 4, and diabetes mellitus (uncontrolled). He was diagnosed with acute ischemic stroke with cranial nerve 7 palsy (with right hemiparesis), acute on chronic kidney disease precipitated by dehydration and ACE inhibitor, and hyperkalemia. Patients with ischemic disease and chronic kidney disaese require constant monitering and careful selected pharmacotherapy. Patient was placed under observation and was prescribed multiple pharamacotherpay to stabalise detoriating condition.

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/adverse effects
Admissions with atrial fibrillation in a multiracial population in Kuala Lumpur, Malaysia

Freestone B, Rajaratnam R, Hussain N, Lip GY

Int J Cardiol, 2003 Oct;91(2-3):233-8.
PMID: 14559136

BACKGROUND: There are established differences in cardiovascular disease in different racial groups. Worldwide, the literature regarding the clinical epidemiology of atrial fibrillation in non-white populations is scarce.
OBJECTIVES: To document the prevalence of atrial fibrillation (AF) in the multiracial population of Malaysia, and to describe the clinical features and management of these patients.
SETTING: Busy city centre general hospital in Kuala Lumpur, Malaysia, over a 1-month period.
SUBJECTS: One-thousand four hundred and thirty-five acute medical admissions, of whom 40 patients (2.8%) had AF.
RESULTS: Of 1435 acute medical admissions to Kuala Lumpur General Hospital over the 4-week study period, 40 had AF (21 male, 19 female; mean age 65 years). Of these, 18 were Malay, 16 Chinese and six Indian. Nineteen patients had previously known AF (seven with paroxysmal AF) and 21 were newly diagnosed cases. The principal associated medical conditions were ischaemic heart disease (42.5%), hypertension (40%) and heart failure (40%). Dyspnoea was the commonest presentation, whilst stroke was the cause of presentation in only two patients. Investigations were under-utilised, with chest X-ray and echocardiography in only 62.5% of patients and thyroid function checked in 15%. Only 16% of those with previously diagnosed AF were on warfarin, with a further three on aspirin. Anticoagulant therapy was started in 13.5% of patients previously not on warfarin, and aspirin in 8%. Records of contraindications to warfarin were unreliable, being identified in only 25%. For those with known AF, 58% were on digoxin. For new onset AF, digoxin was again the most common rate-limiting treatment, initiated in 38%, whilst five patients with new onset AF were commenced on amiodarone. DC cardioversion was not used in any of the patients with new onset AF.
CONCLUSION: Amongst acute medical admissions to a single centre in Malaysia the prevalence of AF was 2.8%. Consistent with previous similar surveys in mainly western (caucasian) populations, standard investigations in this Malaysian cohort were also inadequate and there was underuse of anticoagulation, medication for ventricular rate control and cardioversion to sinus rhythm.

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use
Fulltext Alpha-Glucosidase Inhibitory Effect of Psychotria malayana Jack Leaf: A Rapid Analysis Using Infrared Fingerprinting

Nipun TS, Khatib A, Ahmed QU, Redzwan IE, Ibrahim Z, Khan AYF, et al.

Molecules, 2020 Sep 11;25(18).
PMID: 32932994 DOI: 10.3390/molecules25184161

The plant Psychotria malayana Jack belongs to the Rubiaceae family and is known in Malaysia as "meroyan sakat/salung". A rapid analytical technique to facilitate the evaluation of the P. malayana leaves' quality has not been well-established yet. This work aimed therefore to develop a validated analytical technique in order to predict the alpha-glucosidase inhibitory action (AGI) of P. malayana leaves, applying a Fourier Transform Infrared Spectroscopy (FTIR) fingerprint and utilizing an orthogonal partial least square (OPLS). The dried leaf extracts were prepared by sonication of different ratios of methanol-water solvent (0, 25, 50, 75, and 100% v/v) prior to the assessment of alpha-glucosidase inhibition (AGI) and the following infrared spectroscopy. The correlation between the biological activity and the spectral data was evaluated using multivariate data analysis (MVDA). The 100% methanol extract possessed the highest inhibitory activity against the alpha-glucosidase (IC50 2.83 ± 0.32 μg/mL). Different bioactive functional groups, including hydroxyl (O-H), alkenyl (C=C), methylene (C-H), carbonyl (C=O), and secondary amine (N-H) groups, were detected by the multivariate analysis. These functional groups actively induced the alpha-glucosidase inhibition effect. This finding demonstrated the spectrum profile of the FTIR for the natural herb P. malayana Jack, further confirming its medicinal value. The developed validated model can be used to predict the AGI of P. malayana, which will be useful as a tool in the plant's quality control.

Matched MeSH terms: Enzyme Inhibitors/isolation & purification; Enzyme Inhibitors/chemistry*
Fulltext Alternative RNA Extraction Method in Vibrio vulnificus Infected BrownMarbled Grouper, Epinephelus fuscoguttatus

Fahmeeda Mohamad Jazamuddin, Wan Mohd Aizat, Hoe-Han Goh, Chen-Fei Low, Syarul Nataqain Baharum

Trop Life Sci Res, 2019;30(2):2012-209.
MyJurnal

Vibriosis is a prevalent aquatic disease caused by Vibrio species and has led to massive loss of brown-marbled grouper, Epinephelus fuscoguttatus. The complexity of molecular mechanisms associated with immune defence can be studied through transcriptomics analysis. High quality and quantity of total RNAs are crucial for the veracity of RNA sequencing and gene expression analysis. A low quality RNA will compromise downstream analysis, resulting in loss of time and revenue to re-acquire the data again. Thus, a reliable and an efficient RNA isolation method is the first and most important step to obtain high quality RNA for gene expression studies. There are many aspects need to be considered when deciding an extraction method, such as the cost-effectiveness of the protocol, the duration of chemical exposure, the duration required for a complete extraction and the number of sample-transferring. A good RNA extraction protocol must be able to produce high yield and purity of RNA free from enzyme inhibitors, such as nucleases (RNase), phenols, alcohols or other chemicals carryover, apart from protein and genomic DNA contamination, to maintain isolated RNA integrity in storage condition. In this study, TransZolTM Up produced clean and pure RNA samples from control gills only but not from the infected gill and whole-body tissues. Modified conventional CTAB (conventional hexadecyltrimethylammonium bromide) method was then used as an alternative method to isolate RNA from gill and whole-body tissues of Vibrio-infected E. fuscoguttatus. Modified CTAB method produced intact RNA on gel electrophoresis with higher RIN number (>6.5) for infected gill and whole-body tissues, suggesting that this method could also be used to isolate high quality RNA from fish samples. Therefore, this method is potentially suitable to be used to extract RNA from other fish species especially those that have been infected.

Matched MeSH terms: Enzyme Inhibitors
Andrographolide and 14-deoxy-11, 12-didehydroandrographolide inhibit cytochrome P450s in HepG2 hepatoma cells

Ooi JP, Kuroyanagi M, Sulaiman SF, Muhammad TS, Tan ML

Life Sci, 2011 Feb 28;88(9-10):447-54.
PMID: 21219911 DOI: 10.1016/j.lfs.2010.12.019

Cytochrome P450 (CYP) enzymes have been implicated in a large number of preventable drug-herb interactions. Andrographis paniculata Nees, a tropical herb widely used for various health conditions contains two major diterpenoids, andrographolide and 14-Deoxy-11, 12-Didehydroandrographolide. These compounds were evaluated systematically for their effects on CYP1A2, CYP2D6 and CYP3A4 expressions in HepG2 cells.

Matched MeSH terms: Enzyme Inhibitors/pharmacology*; Cytochrome P-450 Enzyme Inhibitors*
Fulltext Angioedema secondary to angiotensin converting enzyme inhibitors

Thiruventhiran T, Ho BK

JUMMEC, 1999;4(2):113-114.

Angioedema due to whatever cause is potelltially life threatening, especially if it involves the head and neck region. Patients at risk need to be identified and precautionary measures are necessary. The use of Angiotensin Converting Enzyme Inhibitors (ACEIs) has been associated with angioedenia of the face and tongue. Its widespread use has resulted in an increased awareness of this rare but important camplication. We report liere a case of angioedenla secondary to ACEls developing a few months after initiation of therapy and discuss its clinical importance. KEYWORDS: Angioedema, Angiotensin Converting Enzyme Inhibitor.

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors; Enzyme Inhibitors
Angiotensin I-converting enzyme inhibitory activity and bioconversion of isoflavones by probiotics in soymilk supplemented with prebiotics

Yeo SK, Liong MT

Int J Food Sci Nutr, 2010 Mar;61(2):161-81.
PMID: 20085504 DOI: 10.3109/09637480903348122

Lactobacillus sp. FTDC 2113, L. acidophilus FTDC 8033, L. acidophilus ATCC 4356, L. casei ATCC 393, Bifidobacterium FTDC 8943 and B. longum FTDC 8643 were incorporated into soymilk supplemented with fructooligosaccharides (FOS), inulin, mannitol, maltodextrin and pectin. The objective of the present study was to evaluate the effects of prebiotics on the bioactivity of probiotic-fermented soymilk. Proteolytic activity was increased in the presence of FOS, while the supplementation of inulin and pectin increased the angiotensin I-converting enzyme inhibitory activity accompanied by lower IC(50) values. The beta-glucosidase activity was also enhanced in the presence of pectin. This led to higher bioconversion of glucosides to aglycones by probiotics, especially genistin and malonyl genistin to genistein. Results from this study indicated that the supplementation of prebiotics enhanced the in-vitro antihypertensive effect and production of bioactive aglycones in probiotic-fermented soymilk. Therefore, this soymilk could potentially be used as a dietary therapy to reduce the risks of hypertension and hormone-dependent diseases such as breast cancer, prostate cancer and osteoporosis.

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/metabolism; Angiotensin-Converting Enzyme Inhibitors/pharmacology*
Fulltext Angiotensin receptor neprilysin inhibitor as a novel antihypertensive drug: Evidence from Asia and around the globe

Lin DS, Wang TD, Buranakitjaroen P, Chen CH, Cheng HM, Chia YC, et al.

J Clin Hypertens (Greenwich), 2021 03;23(3):556-567.
PMID: 33305531 DOI: 10.1111/jch.14120

Hypertension is a worldwide epidemic that continues to grow, with a subset of patients responding poorly to current treatment available. This is especially relevant in Asia, which constitutes 61% of the global population. Hypertension in Asia is a unique entity that is often salt-sensitive, nocturnal, and systolic predominant. Sacubitril/valsartan is a first-in-class angiotensin receptor neprilysin inhibitor that was first used in heart failure with reduced ejection fraction. Sacubitril inhibits neprilysin, a metallopeptidase that degrades natriuretic peptides (NPs). NPs exert sympatholytic, diuretic, natriuretic, vasodilatory, and insulin-sensitizing effects mostly via cyclic guanosine monophosphate (cGMP)-mediated pathways. As an antihypertensive agent, sacubitril/valsartan has outperformed angiotensin II receptor type 1 blockers (ARBs), with additional reductions of office systolic blood pressures ranging between 5 and 7 mmHg, in multiple studies in Asia and around the globe. The drug was well tolerated even in the elderly or those with chronic kidney disease. Its mechanisms of actions are particularly attractive for treatment of hypertension in Asia. Sacubitril/valsartan offers a novel, dual class, single-molecule property that may be considered as first-line antihypertensive therapy. Further investigations are needed to validate its safety for long-term use and to explore other potentials such as in the management of insulin resistance and obesity, which often coexist with hypertension in Asia.

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors
Fulltext Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers (ARB) Are Protective Against ICU Admission and Mortality for Patients With COVID-19 Disease

ElAbd R, AlTarrah D, AlYouha S, Bastaki H, Almazeedi S, Al-Haddad M, et al.

Front Med (Lausanne), 2021;8:600385.
PMID: 33748156 DOI: 10.3389/fmed.2021.600385

Introduction: Corona Virus disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. The aim of this study was to investigate the impact of being on an Angiotensin-Converting Enzyme Inhibitors (ACEI) and/or Angiotensin Receptor Blockers (ARB) on hospital admission, on the following COVID-19 outcomes: disease severity, ICU admission, and mortality. Methods: The charts of all patients consecutively diagnosed with COVID-19 from the 24th of February to the 16th of June of the year 2020 in Jaber Al-Ahmed Al-Sabah hospital in Kuwait were checked. All related patient information and clinical data was retrieved from the hospitals electronic medical record system. The primary outcome was COVID-19 disease severity defined as the need for Intensive Care Unit (ICU) admission. Secondary outcome was mortality. Results: A total of 4,019 COVID-19 patients were included, of which 325 patients (8.1%) used ACEI/ARB, users of ACEI/ARB were found to be significantly older (54.4 vs. 40.5 years). ACEI/ARB users were found to have more co-morbidities; diabetes (45.8 vs. 14.8%) and hypertension (92.9 vs. 13.0%). ACEI/ARB use was found to be significantly associated with greater risk of ICU admission in the unadjusted analysis [OR, 1.51 (95% CI: 1.04-2.19), p = 0.028]. After adjustment for age, gender, nationality, coronary artery disease, diabetes and hypertension, ICU admission was found to be inversely associated with ACEI use [OR, 0.57 (95% CI: 0.34-0.88), p = 0.01] and inversely associated with mortality [OR, 0.56 (95% CI: 0.33-0.95), p = 0.032]. Conclusion: The current evidence in the literature supports continuation of ACEI/ARB medications for patients with co-morbidities that acquire COVID-19 infection. Although, the protective effects of such medications on COVID-19 disease severity and mortality remain unclear, the findings of the present study support the use of ACEI/ARB medication.

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors
Angiotensin-I Converting Enzyme (ACE) Inhibitory and Anti-Hypertensive Effect of Protein Hydrolysate from Actinopyga lecanora (Sea Cucumber) in Rats

Sadegh Vishkaei M, Ebrahimpour A, Abdul-Hamid A, Ismail A, Saari N

Mar Drugs, 2016 Sep 30;14(10).
PMID: 27706040

Food protein hydrolysates are known to exhibit angiotensin converting enzyme (ACE) inhibitory properties and can be used as a novel functional food for prevention of hypertension. This study evaluated the ACE inhibitory potentials of Actinopyga lecanora proteolysate (ALP) in vivo. The pre-fed rats with ALP at various doses (200, 400, 800 mg/kg body weight) exhibited a significant (p ≤ 0.05) suppression effect after inducing hypertension. To determine the optimum effective dose that will produce maximal reduction in blood pressure, ALP at three doses was fed to the rats after inducing hypertension. The results showed that the 800 mg/kg body weight dose significantly reduced blood pressure without noticeable negative physiological effect. In addition, there were no observable changes in the rats' heart rate after oral administration of the ALP. It was concluded that Actinopyga lecanora proteolysate could potentially be used for the development of functional foods and nutraceuticals for prevention and treatment of hypertension.

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/pharmacology*; Angiotensin-Converting Enzyme Inhibitors/chemistry
Fulltext Angiotensin-I Converting Enzyme (ACE) Inhibitory and Anti-Oxidant Activities of Sea Cucumber (Actinopyga lecanora) Hydrolysates

Ghanbari R, Zarei M, Ebrahimpour A, Abdul-Hamid A, Ismail A, Saari N

Int J Mol Sci, 2015 Dec 04;16(12):28870-85.
PMID: 26690117 DOI: 10.3390/ijms161226140

In recent years, food protein-derived hydrolysates have received considerable attention because of their numerous health benefits. Amongst the hydrolysates, those with anti-hypertensive and anti-oxidative activities are receiving special attention as both activities can play significant roles in preventing cardiovascular diseases. The present study investigated the angiotensin-I converting enzyme (ACE) inhibitory and anti-oxidative activities of Actinopyga lecanora (A. lecanora) hydrolysates, which had been prepared by alcalase, papain, bromelain, flavourzyme, pepsin, and trypsin under their optimum conditions. The alcalase hydrolysate showed the highest ACE inhibitory activity (69.8%) after 8 h of hydrolysis while the highest anti-oxidative activities measured by 2,2-diphenyl 1-1-picrylhydrazyl radical scavenging (DPPH) (56.00%) and ferrous ion-chelating (FIC) (59.00%) methods were exhibited after 24 h and 8 h of hydrolysis, respectively. The ACE-inhibitory and anti-oxidative activities displayed dose-dependent trends, and increased with increasing protein hydrolysate concentrations. Moreover, strong positive correlations between angiotensin-I converting enzyme (ACE) inhibitory and anti-oxidative activities were also observed. This study indicates that A. lecanora hydrolysate can be exploited as a source of functional food owing to its anti-oxidant as well as anti-hypertension functions.

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/pharmacology*; Angiotensin-Converting Enzyme Inhibitors/chemistry*

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