Throughout our evolution, the importance of natural products for medicine and health has been increasing and it continues to be a key source of novel anticancer drugs, leads and new chemical entities. Among natural products, tricyclic heteroaromatic alkaloids such as carbazoles are an important class of natural and semi-synthetic organic compounds. In the last few decades medicinal role of natural and semi-synthetic carbazoles has expanded significantly, especially as a vital heterocyclic class of antitumor agents. Some of the carbazoles that displayed potential anticancer activity have undergone clinical trials. However, complications arising due to multidrug resistance in clinical trials led to very few of the selected carbazoles being approved for cancer therapy. Planar, polycyclic and aromatic carbazoles exhibit anticancer activity via DNA intercalation. Further many carbazoles can be cytotoxic by inhibiting DNA-dependent enzymes such as telomerase and topoisomerase I/II.
Chronic wound infections
caused by antibiotic-resistant bacteria
have become a global health concern. This is attributed to the biofilm-forming
ability of bacteria on wound surfaces, thus enabling their persistent
growth. In most cases, it leads to morbidity and in severe cases mortality.
Current conventional approaches used in the treatment of biofilm wounds
are proving to be ineffective due to limitations such as the inability
to penetrate the biofilm matrix; hence, biofilm-related wounds remain
a challenge. Therefore, there is a need for more efficient alternate
therapeutic interventions. Hydrogen peroxide (HP) is a known antibacterial/antibiofilm
agent; however, prolonged delivery has been challenging due to its
short half-life. In this study, we developed a hydrogel for the codelivery
of HP and antimicrobial peptides (Ps) against bacteria, biofilms,
and wound infection associated with biofilms. The hydrogel was prepared
via the Michael addition technique, and the physiochemical properties
were characterized. The safety,
in vitro
, and
in vivo
antibacterial/antibiofilm activity of the hydrogel
was also investigated. Results showed that the hydrogel is biosafe.
A greater antibacterial effect was observed with HP-loaded hydrogels
(CS-HP; hydrogel loaded with HP and CS-HP-P; hydrogel loaded with
HP and peptide) when compared to HP as seen in an approximately twofold
and threefold decrease in minimum inhibitory concentration values
against methicillin-resistant
Staphylococcus aureus
(MRSA) bacteria, respectively. Similarly, both the HP-releasing
hydrogels showed enhanced antibiofilm activity in the
in vivo
study in mice models as seen in greater wound closure and enhanced
wound healing in histomorphological analysis. Interestingly, the results
revealed a synergistic antibacterial/antibiofilm effect between HP
and P in both
in vitro
and
in vivo
studies. The successfully prepared HP-releasing hydrogels showed
the potential to combat bacterial biofilm-related infections and enhance
wound healing in mice models. These results suggest that the HP-releasing
hydrogels may be a superior platform for eliminating bacterial biofilms
without using antibiotics in the treatment of chronic MRSA wound infections,
thus improving the quality of human health.
The Ebola virus, formally known as the Ebola hemorrhagic fever, is an acute viral syndrome causing sporadic outbreaks that have ravaged West Africa. Due to its extreme virulence and highly transmissible nature, Ebola has been classified as a category A bioweapon organism. Only recently have vaccine or drug regimens for the Ebola virus been developed, including Zmapp and peptides. In addition, existing drugs which have been repurposed toward anti-Ebola virus activity have been re-examined and are seen to be promising candidates toward combating Ebola. Drug development involving computational tools has been widely employed toward target-based drug design. Screening large libraries have greatly stimulated research toward effective anti-Ebola virus drug regimens. Current emphasis has been placed on the investigation of host proteins and druggable viral targets. There is a huge gap in the literature regarding guidelines in the discovery of Ebola virus inhibitors, which may be due to the lack of information on the Ebola drug targets, binding sites, and mechanism of action of the virus. This review focuses on Ebola virus inhibitors, drugs which could be repurposed to combat the Ebola virus, computational methods which study drug-target interactions as well as providing further insight into the mode of action of the Ebola virus.
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