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New synthetic routes were devised for total synthesis of Fe3+‐bound (ferri−) salmycin B (Sal B) (1), glycan‐based Sal analogues 2–5 and their Fe3+‐unbound (desferri−) counterparts 1′–5′ for the structure to activity relationship (SAR) study. The results of SAR study reveal the effective structure of 1 and its desferri‐counterpart 1′ that are responsible for the observed inhibitory activity against Staphylococcus aureus (S. aureus). Among the analogues 2–5 and 2′–5′, glucose‐based analogue 2 and its desferri‐counterpart 2′ exhibited inhibitory potency comparable to 1 and 1′. Chemical modification of 2′ for further antibacterial study enabled us to discover desferri‐Sal analogue 7′ that endowed with a simpler pharmacophore structure but significantly higher antibacterial potency against methicillin‐sensitive and resistant S. aureus than the natural product 1′ and even the clinical vancomycin. Together with a better hydrolytic stability and shorter synthetic route, the analogue 7′ represents an attractive antibiotic lead for further exploration. [ABSTRACT FROM AUTHOR]

Background: The design and synthesis of hybrid molecules will explore finding new drugs. Objectives: The synthesized hybrid molecules to evaluate their biological properties. Methods: Apply click chemistry to tether flavonols and benzenesulfonamide. Results: Two drug candidates show potential against lung cancer. Conclusions: Two drug candidates did not affect the normal cells and provided a new drug design route. [ABSTRACT FROM AUTHOR]