Emerging drug design strategies in anti-influenza drug discovery

Influenza is an acute respiratory infection caused by influenza viruses(IFV),According to the World Health Organization(WHO),seasonal IFV epidemics result in approximately 3-5 million cases of severe illness,leading to about half a million deaths worldwide,along with severe economic losses and social burdens.Unfortunately,frequent mutations in IFV lead to a certain lag in vaccine development as well as resistance to existing antiviral drugs.Therefore,it is of great importance to develop anti-IFV drugs with high efficiency against wild-type and resistant strains,needed in the fight against current and future outbreaks caused by different IFV strains.In this review,we summarize general strategies used for the discovery and development of antiviral agents targeting multiple IFV strains(including those resistant to available drugs).Structure-based drug design,mechanism-based drug design,multivalent interaction-based drug design and drug repurposing are amongst the most relevant strategies that provide a framework for the development of antiviral drugs targeting IFV.

Naphthalimides and analogues as antitumor agents:A review on molecular design, bioactivity and mechanism of action

In this review, we retrospect our progress in biological active naphthalimide and analogues as antitumor agents in the past 20 years. On one hand, various derivations in naphthalimide pharmacophores were developed to enhance their DNA binding affinity and antitumor property thereby. Heterocyclic fused naphthalimides, bis-naphthalimides, non-fused substituted naphthalimides and the carboxamide derivatives were synthesized. For example, thio-heterocyclic fused-naphthalimides were designed and evaluated in comparison with their oxo-heterocyclic fused analogues. Extended or created heterocyclebased skeleton were also developed as antitumor agents. On the other hand, we broaden the design strategy of naphthalimide antitumor agents besides DNA intercalation and topo II poison. We have introduced more drug design methods, such as prodrugs, multitarget drugs, computer-aided drug design,photodynamic therapy. For example, we have got naphthalimide derivatives which inhibited topo II and induced LMP by introducing long alkyl chain and polyamines. Several representative compounds were clarified of their antitumor mechanism of action. In all, our research improves the structure diversity of naphthalimide antitumor agents and distinct variances of antitumor targets and mechanism of action.