Acetylsalicylic acid is used as a non-steroidal anti-inflammatory drugs (NSAID) and antiplatelet agents by inhibiting cyclooxygenases. However, therapy using acetylsalicylic acid could induce gastric bleeding and cause other gastrointestinal toxicity. The aim of this study was to demonstrate the synthesis of a new compound bearing salicylic acid residue namely 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid, to analyze its potential as a ligand for human cyclooxygenase-2 (COX-2) receptor, to evaluate its toxicity level and its effectiveness for analgesic and antiplatelet agent compared with acetylsalicylic acid.Synthesis of 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid was conducted by microwave irradiation. The purity of this compound was evaluated with TLC, IR, NMR, and EDS spectroscopy. The chemical characterization and docking studies against human COX-2 (PDB:5F1A) was performed in-silico. The acute oral toxicity assay was performed under OECD guidelines. The analgesic activity study was performed by plantar and writhing test on animal model. For anti-platelet activity study, we performed tail-bleeding assay and flow cytometry based platelet aggregation assay. We could successfully synthesize a pure white crystalline 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid. In-Silico G-Score result of those compounds gives us preliminary hint of the potential affinity of this compound as a ligand for COX-2 receptor (PDB: 5F1A). Acute toxicity and microscopic gastrointestinal assessments indicated non-observable harmful toxicity parameters. The plantar response time of 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid treated groups showed a significant increment (P < 0.01), and the nociceptive response in writhing test demonstrated a significant dose-dependent decrement. This indicated that its analgesic activity was better than acetylsalicylic acid. The platelet aggregation of 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid was lower than its controls, indicating an aggregation inhibition pattern. The animals treated with 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid gave a longer bleeding time. Overall, this study demonstrated a successful synthesis of pure 2-((3-(chloromethyl)benzoyl)oxy) benzoic acid. We postulated that this compound was better than acetylsalicylic acid, exhibiting excellent analgesic and antiplatelet activity with no toxicity impact.

NOTICE: this is the authors' version of a work that was accepted for publication in Biocatalysis and Agricultural Biotechnology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biocatalysis and Agricultural Biotechnology,

Introduction: Salicylic acid derivate is very popular for its activity to suppress pain, fever, and inflam ma tion. One of its derivatives is acetylsalicylic acid (ASA) wh ich has be en reported repeatedly that, as a nonsteroidal anti-inflam ma tory drug (NSAID), it has a cardioprotective effect. Although ASA has various advantages, several stud ies have reported that it ma y indu ce severe peptic ulcer disease. We recently synthesized a new compoun d derived from salicylic acid, name ly 2-((3-(chloromethyl)be nz oyl)oxy)be nz oic acid (3 -CH 2 Cl) wh ich still has the be nefit of acetylsalicylic acid as an analgesic and antiplatelet, bu t lacks its harmful side effects (Caroline et al., 20 19 ). In addition, in silico stud ies of 3-CH 2 Cl showed a higher affinity towards protein receptor cyclooxygenase-2 (COX-2; PDB: 5F1A ) than ASA. We hypothesized that 3-CH 2 Cl inhibits the COX-2 activity wh ich could presumably decrease the inflam ma tory responses. However, no knowledge is available on the anti-inflam ma tory response and molecular signaling of this new compoun d. Henc e, in this stud y, we investigated the potential func tional relevanc e of 3-CH 2 Cl in regulating the inflamma tory response in lipopolysacch aride (LPS)-indu ced rats. The results of this stud y show that this compoun d could significantly redu ce the inflam ma tory parame ter in LPS-indu ced rats. Material and methods: Rats were indu ced with LPS of 0.5 mg/kg bw intravenously, prior oral administration with vehicle (3 % Pulvi s Gumm i Arabicum / PGA), 50 0 mg/60 kg body weight (b w; rat dosage converted to hu ma n) of 3-CH 2 Cl and ASA. The inflam ma tory parame ters such as ch anges in the temperature of septic shock, cardiac blood plasma concentrations of IL-1β and TNF-α (ELISA), blood inflam ma tion parame ters, wh ite blood cell concentrations, and lung histopathology were observed. Meanwh ile, the stability of 3-CH 2 Cl powder was evaluated. Result: After the administration of 50 0 mg/60 kg bw of 3-CH 2 Cl (rat dosage converted to hu ma n) to LPSindu ced rats, we observed a significant redu ction of both TNF-α (5 .70+ /-1.04 × 10 3 pg/mL, p= <0 .001 ) and IL-1β (2 .32+ /-0.28 × 10 3 pg/mL, p= <0 .001 ) cardiac blood plasma concentrations. Besides, we foun d a redu ction of wh ite blood cell concentration and the severity of lung injury in the 3-CH 2 Cl group compared to the LPS-indu ced rat group. Ad ditionally, this compoun d ma intained the rat body temperature within norma l limits du ring inflam ma tion, preventing the rats to un dergo septic shock, ch aracterized by hypothermic (t = 12 0 min.) or hyperthermic (t = 36 0 min) conditions. Furthermore, 3-CH 2 Cl was foun d to be stable un til 3 years at 25°C with a relative hu midity of 75 ± 5% . Conclusion: 3-CH 2 Cl compoun d inhibited inflam ma tion in the LPS-indu ced inflam ma tion response model in rats, hypothetically through bind ing to COX-2, and presumably inhibited LPS-indu ced NF-κβ signaling pathways. This stud y could be used as a preliminary hint to investigate the t...

Electroactive nanocarbon tags are used in this work to label the DNA primers for the polymerase chain reaction (PCR) amplification of Cauliflower Mosaic Virus 35S promoter sequence, one of the most common markers for the detection of genetically modified organisms (GMOs). The PCR product carrying the electrochemical label can be directly detected on miniaturized electrodes, with the working signal being correlated to the reduction of oxygen-containing groups on the nanocarbon surface. A linear relationship was first established between the electrochemical signal and the nanomaterial concentration, both for the unconjugated electroactive nanocarbon and the conjugates with single-stranded and double-stranded DNA. After which, PCR amplification using a modified sense-primer was performed, and discrimination between amplified products from positive samples (GMO maize) and negative controls (non-GMO maize) was achieved successfully. After the optimization of PCR experimental conditions using the electroactive nanocarbon label, the electrochemical signal recorded as a function of PCR cycle number showed an exponential increase, very similar to that obtained in optical-based real-time PCR. From that, the extrapolated cycle threshold value showed a linear relationship with the initial number of copies of target DNA. Through the findings, electroactive nanocarbon material demonstrated high potential as electrochemical label for PCR, with the electrochemical signals produced directly correlated to the amount of PCR product. This work will serve as a stepping stone for the development of a robust, efficient, and portable electrochemical PCR system, with a reduced cost considering the wide availability and suitability of carbon nanomaterials for mass production, and the cost-effective electrochemical detection.

A locally-adapted, multisensory, psychosocial intervention called Namaste Care program was developed to improve the daily life of persons with advanced dementia (PwAD) through arranging meaningful activities and physical interactions by healthcare staff (Namaste Carers). Congruent with Asian values, the families of PwAD were invited to participate in Namaste Care sessions. The study aimed to explore the influence of Namaste Care on cognitive status and quality of life (QOL) of PwAD, and perceptions and attitudes of caregivers and Namaste Carers toward dementia care were determined. A total of 10 individuals, including patient-caregiver dyads (n = 4) and Namaste Carers (n = 6) participated in a program in a tertiary hospital in Singapore. Quality of Life in Late-Stage Dementia (QUALID) scale and Severe Impairment Rating Scale (SIRS) were employed to evaluate QOL and cognition, respectively, in the pre- and post-survey program in patient-caregiver dyads. Namaste Carers’ knowledge and attitudes toward PwAD were assessed using the Questionnaire on Palliative Care for Advanced Dementia (qPAD). Caregivers and Namaste carers were interviewed post-program separately. A concurrent explanatory mixed-method analysis was done. The mean age of PwAD was 84 years, with 75% (n = 3) patients on enteral tube feeding. Namaste carers were nurses with an average experience of 4.1 years in dementia care. On comparison of pre- and post-program scores of PwAD, QUALID scores showed a decrease (indicating an improvement in the QOL), while the SIRS scores were increased (indicating an improved cognitive response). Namaste Carers scored high on qPAD, reflecting the good understanding and a positive attitude toward PwAD. Thematic analysis of 10 interview transcripts from caregivers and Namaste Carers revealed three themes: the polarizing paradigm of care in advanced dementia; pre-eminence of the Asian family values, and theme of “small actions make a big difference”. Namaste Care served as a bridge between the person-centered care approach and the biomedical model of dementia care. Namaste Care with family participation may be the cornerstone of PwAD to receive culturally-appropriate personalized care and serve as a premise for the operationalization of person-centered care in Asian societies, and undeniably across the world.