Isoquinoline Alkaloids and Their Antiviral, Antibacterial, and Antifungal Activities and Structure-activity Relationship

Background & Objective: The emergence of multidrug-resistant virus, bacteria and fungi has created an urgent need for the development of novel antibiotic drugs from natural products with different mechanism of action. Therefore, in this review, seventeen types of isoquinoline alkaloids, including benzyltetrahydroisoquinoline, benzylisoquinoline, bisbenzylisoquinoline, aporphine, tetrahydroprotoberberine, N-methyltetrahydroprotoberberine, protoberberine, protopine, benzophenanthridine, dihydrobenzophenanthridine, pavine, cularine, phthalideiso-quinoline, spirobenzylisoquinoline, promorphine, morphine and ipecac, were screened and regarded as an attractive target for the discovery of new antiviral, antibacterial and antifungal lead compounds or agents. Method: Notably, sixteen types of alkaloids were biosynthesized from the central precursor benzyltetrahydroisoquinoline in herbal medicine. Finally, the antiviral and antimicrobial activities of 210 isoquinoline alkaloids were uncovered and the structure-activity relationships were also summarized. Conclusion: The quaternary nitrogen and the methylenedioxy at C-2 and C-3 played an important role in increasing the antiviral, antibacterial and antifungal activity of N-methyltetrahydroprotoberberine, protoberberine and benzophenanthridine alkaloids. Keywords: Isoquinoline alkaloids, antiviral, antibacterial, antifungal, antimicrobial, structure-activity relationship, HIV.