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

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( H )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. LD 50 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.

One-pot and divergent synthesis of polysubstituted quinolin-2(1H)-ones and oxireno[2,3-c]quinolin-2(1aH,3H,7bH)-ones via sequential Ugi/Knoevenagel condensation/hydrolysis and Ugi/Corey–Chaykovsky epoxidation reactions

“…All of the reactions were carried out smoothly to give the corresponding quinolin-2(1H)-ones 7, and moderate to good yields were often obtained with various substituents on the reactants (Table 2). As indicated in 4 is Me, i-Pr or Ph) and isocyanides 5 (R 5 is t-Bu, n-Bu or cyclohexyl) can be used in the above onepot cyclization to prepare compounds 7a-7v. For aldehydes 3, the overall yields are related to the R 2 group.…”

“…1). A number of quinolin-2(1 H )-one derivatives have been found to show good anticancer, 1 antiproliferative, 2 antimicrobial, 3 anti-Alzheimer, 4 aldosterone synthase inhibitive 5 and selective androgen receptor modulative activities. 6 The quinolin-2(1 H )-one skeleton also exists in some alkaloids, such as orixiarine and flindersine (Fig.…”

Acute Oral, Subacute, and Developmental Toxicity Profiling of Naphthalene 2-Yl, 2-Chloro, 5-Nitrobenzoate: Assessment Based on Stress Response, Toxicity, and Adverse Outcome Pathways

“…Many naphthalene-based drugs are marketed to treat various diseases, such as rifampicin, naproxen, nafcillin, and bedaquiline (Anwar et al, 2021). After the detailed literature search, it was noted that pharmacological potential of SF5 is only reported in our previous study in which it was analyzed against different Preclinical toxicological studies are mandatory for establishing any molecule/compound for pharmacological and therapeutic purposes as per the standard guidelines (Sayyad et al, 2017).…”

Acute, chronic, and genotoxic studies on the protopine total alkaloids of the Macleaya cordata (willd.) R. Br. in rodents

“…The fetal specimens were observed under a transmission light source using a stereomicroscope, and the number of sternums, incomplete ossification, rib and limb bone abnormalities, Frontiers in Pharmacology frontiersin.org and spinal development (fusion or longitudinal cleft) were examined and recorded in each test group. The other half of the live fetus was placed in Bouin's fixative solution and the fetal viscera were examined after 2 weeks of fixation, and the size, shape and relative position of the organs in different sections of the fetal rat were observed and recorded for abnormalities (Anwar et al, 2021a;2021b).…”