No abstract

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.

Perhatian terhadap faktor-faktor yang mengarah kepada kepatuhan penggunaan antibiotik perlu dilakukan agar masyarakat terhindar dari resistensi. Penelitian ini bertujuan mengidentifikasi faktorfaktor yang mempengaruhi kepatuhan pasien dalam penggunaan antibiotik di 2 apotek di Kota Surabaya. Subjek penelitian prospektif ini adalah masyarakat yang membeli antibiotik di dua apotek, yaitu Apotek Bhumyamca (A) dan Apotek Tiara 2 (B). Data dikoleksi melalui kuisioner teruji, dianalisa dengan statistik deskriptif, dan diuji regresi berganda Hosmer and Lemeshow's. Faktor usia, jenis, penghasilan, durasi dan pola penggunaan antibiotik, informasi antibiotik, keluhan dan tindakan setelah timbul efek samping antibiotik diamati. Sebanyak 94 responden memenuhi kriteria inklusi umumnya wanita, 74% di apotek A dan 68% di apotek B. Penghasilan responden berkisar 2-3 juta rupiah 83% di Apotek A dan 54% di apotek B. Responden menggunakan antibiotik selama 3-5 hari, 47% di Apotek A dan 50% di apotek B. Sebagian besar responden menggunakan antibiotik setelah makan sebanyak 92% di Apotek A dan 88% di apotek B. Informasi antibiotik diperoleh responden dari tenaga kesehatan sebesar 92% di Apotek A dan 85% di apotek B. Responden tidak memiliki keluhan setelah konsumsi antibiotik dengan hasil 87% di Apotek A dan 73% di apotek B. Sebanyak 56% responden di kedua Apotek menghentikan penggunaan antibiotik saat terjadi keluhan sedangkan 44% berobat ke dokter. Responden di Apotek A (86%) dan di apotek B (89%) menunjukkan kepatuhan terhadap instruksi pemakaian saat mengkonsumsi antibiotik. Penelitian menyimpulkan, tidak ada hubungan antara seluruh faktor yang dianalisa terhadap kepatuhan penggunaan antibiotik, kecuali pola penggunaan antibiotik di apotek B (0,011).

Abstract:The new compounds of salicylic acid derivatives, 2-(3-(chloromethyl)

The new compounds of salicylic acid derivatives, 2-(3-(chloromethyl) benzoiloksi) benzoic acid and 2-(4-(chloromethyl) benzoiloksi) benzoate was synthesized to produce a greater analgesic activity and lower stomach irritation from salicylic acid. 2-(4-(chloromethyl) benzoiloksi) benzoic acid and 2-(3-(chloromethyl) benzoiloksi) benzoate was synthesized by Schotten-Baumann acylation reaction. In this study, the analgesic test activity with plantar test method. The compound was given to test animals in doses of 12.5; 25; 50; 100; and 200 mg.kg