Versatile anti-infective properties of pyrido- and dihydropyrido[2,3-d]pyrimidine-based compounds

Bioorg Med Chem. 2023 Jul 15:90:117376. doi: 10.1016/j.bmc.2023.117376.

Ibrahim S Al Nasr ¹, Angela Corona ², Waleed S Koko ³, Tariq A Khan ⁴, Ridha Ben Said ⁵, Ismail Daoud ⁶, Seyfeddine Rahali ⁷, Enzo Tramontano ², Rainer Schobert ⁸, Noureddine Amdouni ⁹, Bernhard Biersack ¹⁰

Affiliations

1 Department of Biology, College of Science and Arts, Qassim University, Unaizah 51911, Saudi Arabia; Department of Science Laboratories, College of Science and Arts, Qassim University, Ar Rass 51921, Saudi Arabia.
2 Laboratorio di Virologia Molecolare, Dipartimento di Scienze della Vita e Dell'Ambiente, Universitá degli Studi di Cagliari, Cittadella Universitaria di Monserrato SS554, 09042 Monserrato, Italy.
3 Department of Science Laboratories, College of Science and Arts, Qassim University, Ar Rass 51921, Saudi Arabia.
4 Department of Clinical Nutrition, College of Applied Health Sciences, Qassim University, Ar Rass 51921, Saudi Arabia.
5 Laboratoire de Caractérisations, Applications et Modélisations des Matériaux, Faculté des Sciences de Tunis, Université Tunis El Manar, Tunis, Tunisia; Department of Chemistry, College of Science and Arts at Ar Rass, Qassim University, Ar Rass 51921, Saudi Arabia.
6 University Mohamed Khider, Department of Matter Sciences, BP 145 RP, Biskra, Algeria; Laboratory of Natural and Bio-active Substances, Faculty of Science, Tlemcen University, P.O. Box 119, Tlemcen, Algeria.
7 Department of Chemistry, College of Science and Arts at Ar Rass, Qassim University, Ar Rass 51921, Saudi Arabia.
8 Organische Chemie I, Universität Bayreuth, Universitätsstrasse 30, 95447 Bayreuth, Germany.
9 Laboratoire de Caractérisations, Applications et Modélisations des Matériaux, Faculté des Sciences de Tunis, Université Tunis El Manar, Tunis, Tunisia.
10 Organische Chemie I, Universität Bayreuth, Universitätsstrasse 30, 95447 Bayreuth, Germany. Electronic address: [email protected].

PMID: 37336083 DOI: 10.1016/j.bmc.2023.117376

Abstract

A series of 1H-indeno[2',1':5,6]dihydropyrido[2,3-d]pyrimidine and 1H-indeno[2',1':5,6]pyrido[2,3-d]pyrimidine derivatives was prepared and screened for antiparasitic and viral RNase H inhibitory activity. Several compounds showed considerable activity against Toxoplasma gondii parasites and Leishmania major amastigotes, which warrants further investigation. Based on the structural similarities of certain derivatives with common viral RNase H inhibitors, a HIV-1 RNase H assay was used to study the RNase H inhibition by selected test compounds. Docking of active derivatives into the active site of the HIV-1 RNase H enzyme was carried out. The new compound 2a, inactive in the antiparasitic tests, showed distinct HIV-1 RNase H inhibition. Thus, ring substitution determines antiparasitic or HIV-1 RNase H inhibitory activity of this promising compound class.

Keywords

Antiparasitic drugs; Antiviral drugs; HIV-1 RNase H; Multi-component reaction; Pyrimidine.

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