Benign-by-Design SAHA Analogues for Human and Animal Vector-Borne Parasitic Diseases

Area of Science:

• Medicinal Chemistry
• Green Chemistry
• Parasitology
• Drug Discovery

Background:

• Urgent need for new drugs aligning with One Health and Green Chemistry principles.
• Cashew nutshell liquid (CNSL) is an abundant agro-industrial waste source.
• Suberoylanilide hydroxamic acid (SAHA) is a known drug, but greener alternatives are sought.

Purpose of the Study:

• To develop novel SAHA analogues from CNSL waste using sustainable methods.
• To evaluate the synthesized compounds for toxicity and antiparasitic activity.
• To investigate the mechanism of action for promising antiparasitic candidates.

Main Methods:

• Synthesis of SAHA analogues (compounds 13-20) from CNSL using a metathesis approach.
• Cytotoxicity assessment on HepG2, IMR-32, and L929 cell lines.
• Screening against major human and animal vector-borne parasitic diseases (VBPDs).
• In silico studies of compound 13 binding to Trypanosoma brucei HDAC (TbDAC).

Main Results:

• Compounds 13-20 were synthesized efficiently and demonstrated no toxicity in vitro.
• Compound 13 exhibited potent activity against the trypomastigote forms of Trypanosoma brucei.
• In silico analysis suggested compound 13 binds to the TbDAC catalytic pocket similarly to SAHA.

Conclusions:

• CNSL-derived SAHA analogues represent a sustainable approach to drug discovery.
• Compound 13 is a promising green hit for treating African sleeping sickness.
• The study provides a foundation for developing new antiparasitic agents from agro-waste.