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In Vitro Screening to Identify Anti-Toxoplasma Compounds and In Silico Modeling for Bioactivities and Toxicity.
Yale J Biol Med 2019; 92(3):369-383YJ

Abstract

Toxoplasmosis, which affects more than a billion people worldwide, is a common parasitic infection caused by the obligate intracellular parasite, Toxoplasma gondii. Current treatment strategies have several limitations, including unwanted side effects and poor efficacy. Therefore, newer therapies are needed for toxoplasmosis. Drug repurposing and screening of a vast array of natural and/or synthetic compounds is a viable option for antiparasitic drug discovery. In this study, we screened 62 compounds comprising natural products (NPs) and FDA-approved (FDA) drugs, to identify the hit compounds that suppress the growth of T. gondii. To determine the parasite inhibitory potential of the compounds, host mammalian cells were infected with a transgenic T. gondii strain, and the viability of the parasite was evaluated by luminescence. Of the 62 compounds, tubericidin, sulfuretin, peruvoside, resveratrol, narasin and diacetoxyscirpenol of the natural product isolates, as well as bortezonib, 10-Hydroxycamtothecin, mebendazole, niflumic acid, clindamycin HCl, mecamylamine, chloroquine, mitomycin C, fenbendazole, daunorubicin, atropine, and cerivastatin of FDA molecules were identified as "hits" with ≥ 40 percent anti-parasite action. Additionally, mitomycin C, radicicol, naringenin, gitoxigenin, menadione, botulin, genistin, homobutein, and gelsemin HCl of the natural product isolates, as well as lomofungin, cyclocytidine, prazosin HCl, cerivastatin, camptothecin, flufenamic acid, atropine, daunorubicin, and fenbendazole of the FDA compounds exhibited cytotoxic activity, reducing the host viability by ≥ 30 percent. Our findings not only support the prospects of drug repurposing, but also indicate that screening a vast array of molecules may provide viable sources of alternative therapies for parasitic infection.

Authors+Show Affiliations

Department of Biochemistry, Medicinal Biochemistry, Nanomedicine & Toxicology Laboratory, Landmark University, Omu-Aran, Nigeria.Department of Chemistry, University of Ilorin, Ilorin, Nigeria.Department of Biochemistry, Medicinal Biochemistry, Nanomedicine & Toxicology Laboratory, Landmark University, Omu-Aran, Nigeria.Department of Biochemistry, Medicinal Biochemistry, Nanomedicine & Toxicology Laboratory, Landmark University, Omu-Aran, Nigeria.Department of Biochemistry, Medicinal Biochemistry, Nanomedicine & Toxicology Laboratory, Landmark University, Omu-Aran, Nigeria.Department of Biochemistry, Medicinal Biochemistry, Nanomedicine & Toxicology Laboratory, Landmark University, Omu-Aran, Nigeria.All Saints University, College of Medicine, Belair, Saint Vincent and the Grenadines.Department of Biochemistry, Medicinal Biochemistry, Nanomedicine & Toxicology Laboratory, Landmark University, Omu-Aran, Nigeria.Department of Microbiology, Landmark University, Omu-Aran, Nigeria.Department of Pharmacology and Therapeutics Department, Faculty of Veterinary Medicine, Damanhour University, Egypt.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31543702

Citation

Adeyemi, Oluyomi Stephen, et al. "In Vitro Screening to Identify Anti-Toxoplasma Compounds and in Silico Modeling for Bioactivities and Toxicity." The Yale Journal of Biology and Medicine, vol. 92, no. 3, 2019, pp. 369-383.
Adeyemi OS, Atolani O, Awakan OJ, et al. In Vitro Screening to Identify Anti-Toxoplasma Compounds and In Silico Modeling for Bioactivities and Toxicity. Yale J Biol Med. 2019;92(3):369-383.
Adeyemi, O. S., Atolani, O., Awakan, O. J., Olaolu, T. D., Nwonuma, C. O., Alejolowo, O., ... Batiha, G. E. (2019). In Vitro Screening to Identify Anti-Toxoplasma Compounds and In Silico Modeling for Bioactivities and Toxicity. The Yale Journal of Biology and Medicine, 92(3), pp. 369-383.
Adeyemi OS, et al. In Vitro Screening to Identify Anti-Toxoplasma Compounds and in Silico Modeling for Bioactivities and Toxicity. Yale J Biol Med. 2019;92(3):369-383. PubMed PMID: 31543702.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In Vitro Screening to Identify Anti-Toxoplasma Compounds and In Silico Modeling for Bioactivities and Toxicity. AU - Adeyemi,Oluyomi Stephen, AU - Atolani,Olubunmi, AU - Awakan,Oluwakemi Josephine, AU - Olaolu,Tomilola Debby, AU - Nwonuma,Charles Obiora, AU - Alejolowo,Omokolade, AU - Otohinoyi,David Adeiza, AU - Rotimi,Damilare, AU - Owolabi,Akinyomade, AU - Batiha,Gaber El-Saber, Y1 - 2019/09/20/ PY - 2019/9/24/entrez PY - 2019/9/24/pubmed PY - 2019/9/24/medline KW - Antiparasite KW - Drug discovery KW - Library of chemical compounds KW - Medicinal biochemistry KW - Parasitic infection SP - 369 EP - 383 JF - The Yale journal of biology and medicine JO - Yale J Biol Med VL - 92 IS - 3 N2 - Toxoplasmosis, which affects more than a billion people worldwide, is a common parasitic infection caused by the obligate intracellular parasite, Toxoplasma gondii. Current treatment strategies have several limitations, including unwanted side effects and poor efficacy. Therefore, newer therapies are needed for toxoplasmosis. Drug repurposing and screening of a vast array of natural and/or synthetic compounds is a viable option for antiparasitic drug discovery. In this study, we screened 62 compounds comprising natural products (NPs) and FDA-approved (FDA) drugs, to identify the hit compounds that suppress the growth of T. gondii. To determine the parasite inhibitory potential of the compounds, host mammalian cells were infected with a transgenic T. gondii strain, and the viability of the parasite was evaluated by luminescence. Of the 62 compounds, tubericidin, sulfuretin, peruvoside, resveratrol, narasin and diacetoxyscirpenol of the natural product isolates, as well as bortezonib, 10-Hydroxycamtothecin, mebendazole, niflumic acid, clindamycin HCl, mecamylamine, chloroquine, mitomycin C, fenbendazole, daunorubicin, atropine, and cerivastatin of FDA molecules were identified as "hits" with ≥ 40 percent anti-parasite action. Additionally, mitomycin C, radicicol, naringenin, gitoxigenin, menadione, botulin, genistin, homobutein, and gelsemin HCl of the natural product isolates, as well as lomofungin, cyclocytidine, prazosin HCl, cerivastatin, camptothecin, flufenamic acid, atropine, daunorubicin, and fenbendazole of the FDA compounds exhibited cytotoxic activity, reducing the host viability by ≥ 30 percent. Our findings not only support the prospects of drug repurposing, but also indicate that screening a vast array of molecules may provide viable sources of alternative therapies for parasitic infection. SN - 1551-4056 UR - https://www.unboundmedicine.com/medline/citation/31543702/In_Vitro_Screening_to_Identify_Anti-Toxoplasma_Compounds_and_In_Silico_Modeling_for_Bioactivities_and_Toxicity DB - PRIME DP - Unbound Medicine ER -