N-Arylsulfonylated C-Homoaporphines as a New Class of Antiplatelet and Antimicrobial Agents
A series of novel N-arylsulfonylated C-homoaporphine alkaloids were synthesized under microwave irradiation and evaluated for their <i>in vitro</i> antiplatelet and antimicrobial activities. Among the series, compounds <b>12a</b>, <b>12c</b>, <b>12e</b>, <b>12f</b>, <b>12h</b>, <b>12j</b>, <b>12k</b>, <b>12m</b>, and <b>12o</b> demonstrated highly potent (∼3-fold) platelet aggregation inhibitory activity than acetylsalicylic acid (IC<sub>50</sub> = 21.34 μg/mL). Several N-arylsulfonylated C-homoaporphines also exhibited promising antimicrobial activity against various strains, including <i>Macrophoma phaseolina</i>, <i>Trichoderma reesei</i>, and <i>Aspergillus niger</i>, with minimum inhibitory concentrations (MIC) of 12.5, 6.25, and 12.5 μg/mL, respectively, comparable to Ketoconazole [MIC = 12.5 μg/mL (MP and AN strain); 6.25 μg/mL (TR strain)]. <b>12h</b> showed potent antibacterial activity (IC<sub>50</sub> = 6.25 μg/mL against <i>Escherichia coli</i> and <i>Bacillus subtilis</i>) compared to Ampicillin (IC<sub>50</sub> = 12.5 μg/mL). After thorough structure-activity relationship (SAR) and <i>in silico</i> studies, C-homoaporphines were identified as a novel class of antiplatelet and antimicrobial agents.
Authors
- Sandeep Chand Chaudhary (ORCID: https://orcid.org/0000-0002-1444-3895)
- Amol T. Mahajan (ORCID: https://orcid.org/0000-0002-1102-8856)
- Rishabh Shrivastava Ronin
- Janmejaya Sen (ORCID: https://orcid.org/0009-0002-1750-1357)
- Bharti Rajesh Kumar Shyamlal (ORCID: https://orcid.org/0000-0001-9553-7692)
- Aarohi Gupta (ORCID: https://orcid.org/0000-0003-1303-1159)
- Vikas Kumar (ORCID: https://orcid.org/0000-0001-9984-0437)
- Manas Mathur (ORCID: https://orcid.org/0000-0003-0970-6096)
Institutions
- University of Massachusetts Amherst (US)
- National Institute of Pharmaceutical Education and Research (IN)
- Malaviya National Institute of Technology Jaipur (IN)
- Gyan Vihar University (IN)
Publication Details
- Journal
- ACS Medicinal Chemistry Letters
- Published
- 2024-12-23
- DOI
- https://doi.org/10.1021/acsmedchemlett.4c00491
- Primary Topic
- Traditional and Medicinal Uses of Annonaceae
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- University Grants Commission
- Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, India
- Malaviya National Institute of Technology, Jaipur
- Science and Engineering Research Board