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Semi-Synthesis of N-Aryl Amide Analogs of Piperine from Piper nigrum and Evaluation of Their Antitrypanosomal, Antimalarial, and Anti-SARS-CoV-2 Main Protease Activities.
Wansri, Rattanaporn; Lin, Aye Chan Khine; Pengon, Jutharat; Kamchonwongpaisan, Sumalee; Srimongkolpithak, Nitipol; Rattanajak, Roonglawan; Wilasluck, Patcharin; Deetanya, Peerapon; Wangkanont, Kittikhun; Hengphasatporn, Kowit; Shigeta, Yasuteru; Liangsakul, Jatupol; Suroengrit, Aphinya; Boonyasuppayakorn, Siwaporn; Chuanasa, Taksina; De-Eknamkul, Wanchai; Hannongbua, Supot; Rungrotmongkol, Thanyada; Chamni, Supakarn.
  • Wansri R; Pharmaceutical Sciences and Technology Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
  • Lin ACK; Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
  • Pengon J; Natural Products and Nanoparticles Research Unit (NP2), Chulalongkorn University, Bangkok 10330, Thailand.
  • Kamchonwongpaisan S; Pharmaceutical Sciences and Technology Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
  • Srimongkolpithak N; Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
  • Rattanajak R; Natural Products and Nanoparticles Research Unit (NP2), Chulalongkorn University, Bangkok 10330, Thailand.
  • Wilasluck P; National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Thailand Science Park, Pathum Thani 12120, Thailand.
  • Deetanya P; National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Thailand Science Park, Pathum Thani 12120, Thailand.
  • Wangkanont K; National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Thailand Science Park, Pathum Thani 12120, Thailand.
  • Hengphasatporn K; National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Thailand Science Park, Pathum Thani 12120, Thailand.
  • Shigeta Y; Center of Excellence for Molecular Biology and Genomics of Shrimp, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
  • Liangsakul J; Molecular Crop Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
  • Suroengrit A; Center of Excellence for Molecular Biology and Genomics of Shrimp, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
  • Boonyasuppayakorn S; Molecular Crop Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
  • Chuanasa T; Center of Excellence for Molecular Biology and Genomics of Shrimp, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
  • De-Eknamkul W; Molecular Crop Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
  • Hannongbua S; Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Ibaraki, Japan.
  • Rungrotmongkol T; Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Ibaraki, Japan.
  • Chamni S; Scientific and Technological Research Equipment Centre, Chulalongkorn University, Bangkok 10330, Thailand.
Molecules ; 27(9)2022 Apr 29.
Article in English | MEDLINE | ID: covidwho-1820341
ABSTRACT
Piper nigrum, or black pepper, produces piperine, an alkaloid that has diverse pharmacological activities. In this study, N-aryl amide piperine analogs were prepared by semi-synthesis involving the saponification of piperine (1) to yield piperic acid (2) followed by esterification to obtain compounds 3, 4, and 5. The compounds were examined for their antitrypanosomal, antimalarial, and anti-SARS-CoV-2 main protease activities. The new 2,5-dimethoxy-substituted phenyl piperamide 5 exhibited the most robust biological activities with no cytotoxicity against mammalian cell lines, Vero and Vero E6, as compared to the other compounds in this series. Its half-maximal inhibitory concentration (IC50) for antitrypanosomal activity against Trypanosoma brucei rhodesiense was 15.46 ± 3.09 µM, and its antimalarial activity against the 3D7 strain of Plasmodium falciparum was 24.55 ± 1.91 µM, which were fourfold and fivefold more potent, respectively, than the activities of piperine. Interestingly, compound 5 inhibited the activity of 3C-like main protease (3CLPro) toward anti-SARS-CoV-2 activity at the IC50 of 106.9 ± 1.2 µM, which was threefold more potent than the activity of rutin. Docking and molecular dynamic simulation indicated that the potential binding of 5 in the 3CLpro active site had the improved binding interaction and stability. Therefore, new aryl amide analogs of piperine 5 should be investigated further as a promising anti-infective agent against human African trypanosomiasis, malaria, and COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Piper nigrum / Alkaloids / COVID-19 / Antimalarials Type of study: Experimental Studies Limits: Animals / Humans Language: English Journal subject: Biology Year: 2022 Document Type: Article Affiliation country: Molecules27092841

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Piper nigrum / Alkaloids / COVID-19 / Antimalarials Type of study: Experimental Studies Limits: Animals / Humans Language: English Journal subject: Biology Year: 2022 Document Type: Article Affiliation country: Molecules27092841