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

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

Fareeha Anwar  1   2 , Uzma Saleem  3 , Atta Ur Rehman  4 , Bashir Ahmad  1   2 , Tariq Ismail  5 , Muhammad Usman Mirza  6   7 , Lee Yean Kee  8 , Iskandar Abdullah  8 , Sarfraz Ahmad  8
Affiliations

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

Fareeha Anwar et al. ACS Omega. .

Retraction in

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.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Chemical structure of the test compound SF3.
Figure 2
Figure 2
Effects of treatments on body weights (g) in acute oral, subacute, and teratogenicity studies.
Figure 3
Figure 3
Effects of SF3 (40 mg/kg) treatment on skeletal anomalies during teratogenicity studies; (A) No ribs fusion, (B) no shortening of normal ossified bones of forelimbs, (C) no shortening of completely ossified hind limb bones, (D) normal vertebral column, (E) normal bone sizes, (F) no cleft palate, (G) normal tail, and (H) normal lower vertebral column bones.
Figure 4
Figure 4
Soft tissue examination of animals pubs treated with SF3 (40 mg/kg). (A) Normal intestine, (B1) normal head section, (B2) olfactory bulb, (B3) retina, (B4,C) two representation of the normal palate, (D) no hydronephrosis, (E) normal kidney size with no hydronephrosis, (F) normal frontal lobe section, (G) normal heart size, and (H) normal liver size.
Figure 5
Figure 5
Sperm morphology after the treatment with selected doses of SF3 in subacute toxicity studies.
Figure 6
Figure 6
Biochemical parameter estimation after 28 days of treatment with different dose levels of SF3 in the subacute study. Data are represented as mean ± SEM, n = 10. **P < 0.01 and ***P < 0.001 were given in comparison with the control.
Figure 7
Figure 7
Estimation of oxidative stress markers in the selected organs of male and female rats during the subacute toxicity study. The data are presented as mean ± SEM of n = 3 where *P < 0.05 is the level of significance during increase and ^P < 0.05 is the level of significance during decrease in comparison with the control.
Figure 8
Figure 8
Serum histamine and testosterone levels in the subacute toxicity study. The data are presented as mean ± SEM of n = 3, where **P < 0.01 is the significance level compared to the control.
Figure 9
Figure 9
Histopathological studies on selected organs in control, acute oral toxicity, and teratogenicity studies.
Figure 10
Figure 10
Histopathological studies on selected organs of female animals in subacute toxicity studies.
Figure 11
Figure 11
Histopathological studies on selected organs of male animals in subacute toxicity studies.
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References

    1. Wang S.-J.; Wang Z.; Tang Y.; Chen J.; Zhou L. Asymmetric Synthesis of Quinoline-Naphthalene Atropisomers by Central-to-Axial Chirality Conversion. Org. Lett. 2020, 22, 8894–8898. 10.1021/acs.orglett.0c03285. - DOI - PubMed
    1. Lazzara P. R.; Jain A. D.; Maldonado A. C.; Richardson B.; Skowron K. J.; David B. P.; Siddiqui Z.; Ratia K. M.; Moore T. W. Synthesis and Evaluation of Noncovalent Naphthalene-Based KEAP1-NRF2 Inhibitors. ACS Med. Chem. Lett. 2020, 11, 521–527. 10.1021/acsmedchemlett.9b00631. - DOI - PMC - PubMed
    1. Makar S.; Saha T.; Singh S. K. Naphthalene, a versatile platform in medicinal chemistry: Sky-high perspective. Eur. J. Med. Chem. 2019, 161, 252–276. 10.1016/j.ejmech.2018.10.018. - DOI - PubMed
    1. Unzner T. A.; Grossmann A. S.; Magauer T. Rapid Access to Orthogonally Functionalized Naphthalenes: Application to the Total Synthesis of the Anticancer Agent Chartarin. Angew. Chem. 2016, 55, 9763–9767. 10.1002/anie.201605071. - DOI - PubMed
    1. Zhang H.-J.; Rumschlag-Booms E.; Guan Y.-F.; Wang D.-Y.; Liu K.-L.; Li W.-F.; Nguyen V. H.; Cuong N. M.; Soejarto D. D.; Fong H. H. S.; Rong L. Potent Inhibitor of Drug-Resistant HIV-1 Strains Identified from the Medicinal PlantJusticia gendarussa. J. Nat. Prod. 2017, 80, 1798–1807. 10.1021/acs.jnatprod.7b00004. - DOI - PubMed

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