Background: Hypertension is a worldwide epidemic that has been recognized as the most leading global risk for mortality, with its prevalence associated with increased blood pressure, concomitant risks of cardiovascular and kidney diseases, and major commonality in individuals advanced in age. With the current treatment options for hypertension management, there is still a need to develop therapies that directly target receptors that aid in hypertension treatment. Methodology: The study focused on the in-silico profiling of the reported compounds from Areca catechu L. (fam. Arecaceae) towards the n-domain and c-domain angiotensin converting enzyme (ACE) receptor models. Bioisosteric replacement was used to create bioisosteres investigated for similar binding affinity. Results: Some A. catechu compounds exhibited favorable binding energies towards the n- and c-domain receptor models of ACE, binding in the same ACE ligand binding site as lisinopril, benazepril, and sampatrilat via similar interactions and amino acid residues. The majority of A. catechu compounds with favorable ACE binding energies belong to the phytochemical classes of flavonoids, polyphenols and phenolics, glycosides, and steroids. After in silico toxicity and pharmacokinetic profiling, the bioisosteres Leuco-DM02-39, Leuco-DM02-66, Leuco-DM05-60, Querc-DM09-63, and Querc-DM14-31 with binding energies higher than their parent compounds and comparable to lisinopril, benazepril, and sampatrilat were deemed the best. Conclusion A. catechu compounds have the potential to target ACE n-domain and c-domain receptor models. Three leucocyanidin and two quercetin bioisosteres exhibited favorable binding to the n-domain and c-domain ACE receptor models and could be further optimized to derive a promising antihypertensive agent through ACE inhibition.
Peptidyl-Dipeptidase A ; Areca ; Hypertension

Quercetin, a flavonoid compound which is widely distributed in plants are considered ass beneficial physiologically due to attributed bioactivity such as anti-cancer, immunomodulatory, antidiabetic, and anti-inflammatory. In this study, the quercetin content from the dried Blumea balsamifera L. DC dried leaf was macerated with 95% ethanol and the concentrated extract was purified using Modified Kupchan method and flash chromatography. All fractions were tested for the presence of flavonoids using phytochemical screening and the selected dichloromethane fraction were further purified using another round of flash chromatograph. All resulting fractions and pooled samples were tested for the antioxidant property using the developed Thin Layer Chromatography (TLC)-Bioautography and separated compounds were derivatized with DPPH. Using the optimized TLC-Bioautography method, the quercetin content in the dichloromethane fraction was analyzed and compared with a reversed phase high performance liquid chromatography hyphenated with photodiode array detector (RP-HPLC-PDA). The calculated quercetin content from the pooled sample using TLC-bioautography method is 2.25 mg/ml and from RP-HPLC-PDA is 2.02 mg/ml which was not comparable statistically using unpaired t-test (p<0.05, α=0.05
Quercetin

Background: Breast cancer is one of the leading causes of deaths in women worldwide, affecting nearly 7.8 million people. In 2020 in the Philippines, there were around 150,000 Filipinos who were newly diagnosed with the disease. The complex pathogenesis of breast cancer in addition to the emergence of resistance to therapy makes the treatment very challenging. Compounds that can antagonize the effects of estradiol towards ER-α, especially the mutant Y537S type are sought for. Objectives: The focus of this study was the in-silico assessment of the reported secondary metabolites from Phaseolus vulgaris L. (fam. Fabaceae) towards the wild-type and mutant ER-α. Bioisosteric replacement was conducted to generate analogs that can possibly have a comparable binding affinity as estradiol towards estrogen receptors alpha. Results: Majority of the secondary metabolites present in Phaseolus vulgaris L. belong to the group of phytoestrogens, phytosterols, and plant hormones. These groups of compounds exhibited favorable binding energies toward the wild-type and mutant (Y537S) estrogen receptors alpha. Moreover, they bind to the same ligand binding pocket as estradiol, involving similar interactions and amino acid residues. Conclusion Compounds from Phaseolus vulgaris L. can potentially target ER-α. Four gibberellin A19 analogs were generated that exhibited favorable binding towards the wild- and mutant- ER-α and may be further optimized to obtain a promisin gcompound against breast cancer.
Breast Neoplasms ; Molecular Docking Simulation

BACKGROUND

Drug use and abuse is a public health issue that has come into focus in the Philippines in the past years. Excluding the years of the COVID-19 pandemic, there has been a yearly increase in the number of admissions to treatment and rehabilitation centers. The census in the University of the Philippines-Philippine General Hospital (UP-PGH) National Poison Management and Control Center (NPMCC) shows a parallel increase in drug-positive patients consulting in the emergency room (ER).

The objective of this study was to describe the demographic, clinical, and drug use profiles of substance users admitted to the UP-PGH and referred to the NPMCC for drug testing.

This is a cross-sectional study where participants included patients aged 10 years and above who were referred to the NPMCC for drug testing within three days of the ER consult. Once consent or assent from children was obtained, patients were interviewed and examined. Urine samples were collected for drug screening using drugs of abuse screening test kits. A split sample was sent to the UP Drugs of Abuse Research Laboratory (UP DARL) for analysis using the liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). The data was encoded in the REDcap platform. The results were analyzed and summarized using descriptive statistics.

Three hundred eighty-four (384) individuals participated in the study and submitted urine samples for testing from 1 January 2019 to 28 February 2020. One hundred thirty-four (134) samples were positive for substances of abuse detected by drug screening test kits for methamphetamine (MAP), delta-9-tetrahydrocannabinol (THC), cocaine, 3,4-methylenedioxymethamphetamine (MDMA), benzodiazepines, and opioids, and by LC-QTOF/ MS analysis. Majority of the patients were males with an average age of 34.54 ± 1.16 years old. Many complained of neurobehavioral changes necessitating consultation at the hospital emergency room. The neurologic and cardiovascular systems were frequently affected. By using the drugs of abuse test kit, methamphetamine was the most common substance of abuse detected and was seen in 40.3% of the samples. Amphetamine type stimulants were the most common group of drugs identified by LC-QTOF/ MS analysis and was seen in 103 instances. New psychoactive substances detected more frequently than others include paramethoxymethamphetamine (PMMA), 3,4- methylenedioxy methamphetamine (MDMA) and 3,4- methylenedioxyamphetamine (MDA). A few cathinones like butylone and cathinone were also detected.

Methamphetamine was the most common substance of abuse detected in urine samples of the participants. New psychoactive substances were also detected in urine samples when LC-QTOF/MS analysis was utilized. Most persons who use drugs are unemployed young- to mid-adult males. The participants often had neurobehavioral and cardiovascular signs and symptoms.