- Medicinal Chemistry
Location: Webinar
Chair
Osarumwense Peter Osarodion
Ondo State University of Science and Technology, Nigeria
Session Introduction
Osarumwense Peter Osarodion
Ondo State University of Science and Technology, Nigeria
Title: Synthesis, analgesic activity of 3-amino 4,5-dimethoxyl-2-methyl quinazolin-4(3H)-one an amino-6-methoxyl-2-methyl of 4H–benzo[d] [1,3]–oxazine–4–one
Biography:
Osarumwense Peter Osarodion has completed his PhD at the age of 35 years from the University of Benin, Benin City, Edo State, Nigeria. He is the Lecturer of Ondo State University of Science and Technology. He has published more than 40 papers in reputed journals and has been serving as an editorial board member of repute.
Abstract:
Introduction: The rapid a d appearance of antibiotic resistant strains t ns today and m nd misuse of antibiotics and more Quinazolinone ring sy ng system was rewarded as a s a promising m ng molecule because of its br s broad spectrum of biological activities like anti-histaminic, a , anticancer [2,3], anti-HIV [4], anti-inflammatory,[5]analgesic, [6] anti-diabetic [7], anti-bacterial [8], antifungal [9], anti-oxidant [10], a , anti-tubercular [11], anti-convulsant[12].
Objectives: These objectives of this st s study w udy was to e o eliminate the current challenges by syn by synthesizing these novel antibacterial quinazolinone derivatives with a h a high a gh antibacterial potential. Methods: The condensation of 2-amino-methyl-3,4-dimethoxybenzoate with acetic anhydride yielded the cyclic compound 2-methyl-5-substituted-1,3-benzo-oxazine-4-one which further produced a novel 2,3-disubstituted quinazolin-4 ones via the reaction with hydrazine hydrate. The compounds synthesized were unequivocally confirmed by means of Infrared, Nuclear Magnetic Resonance (1H and 13C), Gas chromatography-mass spectrophotometer and elemental analysis. The synthesized compounds w pounds were screened against various st ous strains of microorganism; Staphylococcus aureus, Bacillus spe s species, Escherichia coli, Klebsiella pne a pneumonia, Serratia marcescens, and candida al da albicans. Results: Compounds 1 a pounds 1 a pounds 1 and 2 show nd 2 show nd 2 showed significant activity a y against Staphylococcus aureusand Se usand Serratia marcescenswith MI h MIC ranging f ng from 6 – 12 m 6 – 12 m 6 – 12 m 6 12 mg/mL. Discussion: Compound 1 displayed a singlet signal at: δ 3.78 attributed to methoxyl group and singlet at δ 3.68 which was due to methyl group. Also, 1H NMR spectrum of compound 2 showed a characteristic signal at δ 2.56 (singlet) corresponding to methyl group and duplet at: δ 3.90 for methoxy group. For the IR spectra, Compound 1 was characterized by absence of v NH2and presence of v C-O stretch in 1101cm-1 region of the compound. Compound 2 showed the highest antibacterial activity at 16 mm compared to compound 1 and Ciprofloxicin (CPX) for bacteria, Ketonaxol (PEF). The compounds synthesized had a higher activity than Ciprofloxicin (CPX) for bacteria, Ketonaxol (PEF) for fungus, a standard antibacterial drug.
Conclusion: Compound 2 had a higher antibacterial activity than Compound 1. The compounds synthesized had a higher activity than Ciprofloxicin (CPX) for bacteria, Ketonaxol (PEF) for fungus, a standard antibacterial drug.
Keywords: Antibacterial activity, Q y, Quinazoline-4(3H)-One, 6-methoxyl 2-methyl 4H–benzo[d] [1,3]–oxazine– 4–One, N , Nucleophile, Synthesis, 3, 3-Amino 6- no 6-methoxyl -2-Methyl
Kouki Shinohara
Institute of Science Tokyo, Japan
Title: Structure activity relationship studies of novel SARS-CoV-2 papain-like protease inhibitors
Biography:
Kouki Shinohara earned his Bachelor's degree in Chemistry from Kitami University and his Master's degree in Medical Engineering and Health Sciences from Tokyo Medical and Dental University. He is currently a doctoral student in Biomedical Engineering and Medical Science at the same university, focusing on developing novel inhibitors for SARS-CoV-2 under the guidance of Professor Hirokazu Tamura. He is also a Science Tokyo Spring Fellow.
Abstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has not yet been eradicated. SARS-CoV-2 has two types of proteases, a main protease (Mpro) and a papain-like protease (PLpro). Papain-like protease (PLpro) is a viral protease essential for SARS-CoV-2 replication in concurrence with a main protease. The active site of PLpro from SARS-CoV, the causative virus of the Severe Acute Respiratory Syndrome (SARS) outbreak in 2002, exhibits 100% homology to that of SARS-CoV-2 PLpro. Dr. Mitsuya and colleagues found that a SARS-CoV PLpro inhibitor, GRL-0048, showed inhibitory potency against SARS-CoV-2. Therefore, we started structure-activity relationship (SAR) studies using GRL-0048 as a lead compound to develop more potent SARS-CoV-2 PLpro inhibitors. We previously developed several potent SARS-CoV-2 Mpro inhibitors, including TKB245 and TKB248, by introducing fluorine atoms into lead compounds to induce an effective fluorine-associated interaction with Mpro and enhance cell-membrane permeability. In this study, we designed and synthesized novel compounds using GRL-0048 as a lead compound. A docking simulation of GRL-0048 with SARS- CoV-2 PLpro identified suitable sites for fluorine substitutions at suitable sites in the inhibitor molecules where there is space for the interaction with SARS-CoV-2 PLpro. Structure-activity relationship studies led to the development of several inhibitors exhibiting superior potency compared to GRL-0048.