Antimycobacterial activity of natural products and synthetic agents: Pyrrolodiquinolines and vermelhotin as anti-tubercular leads against clinical multidrug resistant isolates of Mycobacterium tuberculosis

• Natural products and synthetic compounds were tested against MDR TB isolates.
• Vermelhotin, a natural tetramic acid, exhibited potent antimycobacterial activity.
• One-pot synthesis of pyrrolodiquinoline was achieved under microwave irradiation.
• Pyrrolodiquinolines displayed potent anti-tubercular activity (MDR TB isolates).

Various classes of natural products and synthetic compounds were tested against reference strains and clinical multidrug resistant isolates of Mycobacterium tuberculosis. Vermelhotin (19), a natural tetramic acid from fungi, was the most active toward clinical MDR TB isolates (MIC 1.5–12.5 μg/mL). Synthetic compounds (i.e. benzoxazocines, coumarins, chromenes, and pyrrolodiquinoline derivatives) were prepared by green chemistry approaches. Under microwave irradiation, a one-pot synthesis of pyrrolodiquinoline 85 was achieved by homocoupling of 1-methylquinolinium iodide; the structure of 85 was confirmed by single-crystal X-ray analysis. Compound 85 and its derivative 86 exhibited potent anti-tubercular activity (MIC 0.3–6.2 μg/mL) against clinical MDR TB isolates, and they displayed weak cytotoxicity toward normal cell line. The scaffold of 85 and 86 is potential for antimycobacterial activity.

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