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4-苯基-3,4-二氢苯并[]喹啉-2(1)-酮的毒理学筛选:一种治疗阿尔茨海默病的新潜在候选药物

Toxicological Screening of 4-Phenyl-3,4-dihydrobenzo[]quinolin-2(1)-one: A New Potential Candidate for Alzheimer's Treatment.

作者信息

Anwar Fareeha, Saleem Uzma, Rehman Atta Ur, Ahmad Bashir, Ismail Tariq, Mirza Muhammad Usman, Kee Lee Yean, Abdullah Iskandar, Ahmad Sarfraz

机构信息

Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore 54000 Pakistan.

Riphah Institute of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Riphah International University, Islamabad 44000, Pakistan.

出版信息

ACS Omega. 2021 Apr 16;6(16):10897-10909. doi: 10.1021/acsomega.1c00654. eCollection 2021 Apr 27.

Abstract

Toxicity studies are necessary for the development of a new drug. Naphthalene is a bicyclic molecule and is easy to derivatize. In our previous study, a derivative of naphthalene (4-phenyl,3,4-dihydrobenzoquinoline-2()one) was synthesized and reported its in vitro activity on different enzymes. This study was a probe to investigate the toxicity potential of that compound (SF3). Acute oral (425), subacute (407), and teratogenicity (414) studies were planned according to their respective guidelines given by organization of economic cooperation and development (OECD). Acute oral, subacute, and teratogenicity studies were carried out on 2000, 5-40, and 40 mg/kg doses. Blood samples were collected for hematological and biochemical analyses. Vital organs were excised for oxidative stress (superoxide dismutase, catalase, glutathione, and malondialdehyde) and histopathological analysis. of SF3 was higher than 2000 mg/kg. In acute and subacute studies, levels of alkaline phosphates and aspartate transaminase were increased. Teratogenicity showed no resorptions, no skeletal or soft tissue abnormalities, and no cleft pallet. Oxidative stress biomarkers were close to the normal, and no increase in the malondialdehyde level was seen. Histopathological studies revealed normal tissue architecture of the selected organs, except kidney, in acute oral and subacute toxicity studies at 40 mg/kg. The study concluded that SF3 is safer if used as a drug.

摘要

毒性研究对于新药开发至关重要。萘是一种双环分子,易于衍生化。在我们之前的研究中,合成了一种萘衍生物(4-苯基,3,4-二氢苯并喹啉-2()酮),并报道了其对不同酶的体外活性。本研究旨在探究该化合物(SF3)的潜在毒性。根据经济合作与发展组织(OECD)给出的各自指南,计划进行急性口服(425)、亚急性(407)和致畸性(414)研究。急性口服、亚急性和致畸性研究分别以2000、5 - 40和40 mg/kg的剂量进行。采集血样进行血液学和生化分析。切除重要器官进行氧化应激(超氧化物歧化酶、过氧化氢酶、谷胱甘肽和丙二醛)和组织病理学分析。SF3的半数致死量高于2000 mg/kg。在急性和亚急性研究中,碱性磷酸酶和天冬氨酸转氨酶水平升高。致畸性研究显示无吸收、无骨骼或软组织异常,也无腭裂。氧化应激生物标志物接近正常,丙二醛水平未见升高。组织病理学研究表明,在40 mg/kg的急性口服和亚急性毒性研究中,除肾脏外,所选器官的组织结构正常。该研究得出结论,SF3作为药物使用更安全。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ed/8153932/a5022c7ad64f/ao1c00654_0002.jpg

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