Crystallographic study, biological assessment and POM/Docking studies of pyrazoles-sulfonamide hybrids (PSH): Identification of a combined Antibacterial/Antiviral pharmacophore sites leading to in-silico screening the anti-Covid-19 activity

Mohammed Chalkha; Asmae Nakkabi; Taibi Ben Hadda; Malika Berredjem; Abdelfattah El Moussaoui; Mohamed Bakhouch; Mohamed Saadi; Lahcen El Ammari; Faisal A Almalki; Hamid Laaroussi; Violeta Jevtovic; Mohamed El Yazidi

doi:10.1016/j.molstruc.2022.133605

Crystallographic study, biological assessment and POM/Docking studies of pyrazoles-sulfonamide hybrids (PSH): Identification of a combined Antibacterial/Antiviral pharmacophore sites leading to in-silico screening the anti-Covid-19 activity

J Mol Struct. 2022 Nov 5:1267:133605. doi: 10.1016/j.molstruc.2022.133605. Epub 2022 Jun 28.

Authors

Affiliations

¹ Engineering Laboratory of Organometallic and Molecular Materials and Environment (LIMOME), Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, P.O. Box 1796, Atlas, Fez, 30000, Morocco.
² Laboratoire de Chimie des Matériaux et Biotechnologie des Produits Naturels, Faculté des Sciences, Université Moulay Ismail, BP 11201, Meknes 50000, Morocco.
³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
⁴ Laboratory of Applied Chemistry & Environment, Faculty of Sciences, Mohammed Premier University, MB 524, Oujda 60000, Morocco.
⁵ Laboratoire de chimie organique appliquée (LCOA), Groupe de Synthèse de biomolécules et modélisation moléculaire, Université Badji-Mokhtar Annaba, BP 12, Annaba 23000, Algérie.
⁶ Laboratory of Biotechnology, Environment, Agri-Food, and Health (LBEAS), Faculty of Sciences, University Sidi Mohamed Ben Abdellah (USMBA), Fez 30050, Morocco.
⁷ Laboratory of Bioorganic Chemistry, Department of Chemistry, Faculty of Sciences, Chouaïb Doukkali University, El Jadida 24000, Morocco.
⁸ Laboratoire de Chimie Appliquée des Matériaux, Centres des Sciences des Matériaux, Faculty of Science, Mohammed V University, Avenue Ibn Battouta, BP. 1014, 100090 Rabat, Morocco.
⁹ Department of Chemistry, College of Science, University of Hail, Hail 81451, Saudi Arabia.

Abstract

The discovery and development of new potent antimicrobial and antioxidant agents is an essential lever to protect living beings against pathogenic microorganisms and free radicals. In this regard, new functionalized pyrazoles have been synthesized using a simple and accessible approach. The synthesized aminobenzoylpyrazoles 3a-h and pyrazole-sulfonamides 4a-g were obtained in good yields and were evaluated in vitro for their antimicrobial and antioxidant activities. The structures of the synthesized compounds were determined using IR, NMR, and mass spectrometry. The structure of the compound 4b was further confirmed by single crystal X-ray diffraction. The results of the in vitro screening show that the synthesized pyrazoles 3 and 4 exhibit a promising antimicrobial and antioxidant activities. Among the tested compounds, pyrazoles 3a, 3f, 4e, 4f, and 4g have exhibited remarkable antimicrobial activity against some microorganisms. In addition, compounds 3a, 3c, 3e, 4a, 4d, 4f, and 4g have shown a significant antioxidant activity in comparison with the standard butylhydroxytoluene (BHT). Hence, compounds 3a, 4f, and 4g represent interesting dual acting antimicrobial and antioxidant agents. In fact, pyrazole derivatives bearing sulfonamide moiety (4a-g) have displayed an important antimicrobial activity compared to pyrazoles 3a-h, this finding could be attributed to the synergistic effect of the pyrazole and sulfonamide pharmacophores. Furthermore, Molecular docking results revealed a good interaction of the synthesized compounds with the target proteins and provided important information about their interaction modes with the target enzyme. The results of the POM bioinformatics investigations (Petra, Osiris, Molinspiration) show that the studied heterocycles present a very good non toxicity profile, an excellent bioavailability, and pharmacokinetics. Finally, an antiviral pharmacophore (O ^δ-, O ^δ-) was evaluated in the POM investigations and deserves all our attention to be tested against Covid-19 and its Omicron and Delta mutants.

Keywords: Antimicrobial/Antioxidant bioactivity; Docking study; Identification of the pharmacophore sites; POM, Petra/Osiris/Molinspiration; PSH, Pyrazoles-Sulfonamide Hybrids; Petra/Osiris/Molinspiration (POM) analyses; Pyrazole Linked Sulfonamide Conjugates.