Novel Isoniazid-Based 1,3,4-Oxadiazole-Fatty Acid Hybrids: Synthesis, In Vitro Biological Activity and In Silico...

Area of Science:

• Medicinal Chemistry
• Drug Discovery
• Organic Synthesis

Background:

• Cancer and multidrug-resistant (MDR) bacterial infections are significant global health challenges.
• Development of novel bioactive compounds is crucial for addressing these unmet medical needs.

Purpose of the Study:

• To design and synthesize new fatty acid derivatives incorporating an oxadiazole moiety and isoniazid.
• To evaluate the synthesized compounds for anticancer and antimicrobial activities.

Main Methods:

• Synthesis of novel isoniazid-oxadiazole-fatty acid hybrids.
• Structural confirmation using NMR, IR, and mass spectrometry.
• In vitro anticancer screening against B16-F10 cell line and preliminary antibacterial/antifungal assays.

Main Results:

• Compounds 7b and 7e exhibited significant cytotoxic activity against B16-F10 cells.
• Compound 7b demonstrated potent and selective anticancer activity (IC50 = 7.3 ± 0.8 µM in cancer cells vs. 18.4 ± 0.2 µM in normal cells).
• Synthesized derivatives showed moderate antibacterial and antifungal effects, alongside favorable predicted pharmacokinetic and safety profiles (TOPKAT).

Conclusions:

• The novel isoniazid-oxadiazole-fatty acid hybrids are promising dual-acting therapeutic candidates.
• Compound 7b shows particular promise as a selective anticancer agent.
• Further development of these compounds is warranted for potential therapeutic applications.