The antimalarial activity of 1,2,4-trioxolane/trioxane hybrids and dimers: A review.

Malaria, a mosquito-borne parasitic infection caused by protozoan parasites belonging to the genus Plasmodium, is a dangerous disease that contributes to millions of hospital visits and hundreds and thousands of deaths across the world, especially in Sub-Saharan Africa. Antimalarial agents are vital for treating malaria and controlling transmission, and 1,2,4-trioxolane/trioxane-containing agents, especially artemisinin and its derivatives, own antimalarial efficacy and low toxicity with unique mechanisms of action. Moreover, artemisinin-based combination therapies were recommended by the World Health Organization as the first-line treatment for uncomplicated malaria infection and have remained as the mainstay of the treatment of malaria, demonstrating that 1,2,4-trioxolane/trioxane derivatives are useful prototypes for the control and eradication of malaria. However, malaria parasites have already developed resistance to almost all of the currently available antimalarial agents, creating an urgent need for the search of novel pharmaceutical interventions for malaria. The purpose of this review article is to provide an emphasis on the current scenario (January 2012 to January 2022) of 1,2,4-trioxolane/trioxane hybrids and dimers with potential antimalarial activity and the structure-activity relationships are also discussed to facilitate further rational design of more effective candidates.

Indole Alkaloids, Synthetic Dimers and Hybrids with Potential In Vivo Anticancer Activity.

Indole, a heterocyclic organic compound, is one of the most promising heterocycles found in natural and synthetic sources since its derivatives possess fascinating structural diversity and various therapeutic properties. Indole alkaloids, synthetic dimers and hybrids could act on diverse targets in cancer cells, and consequently, possess potential antiproliferative effects on various cancers both in vitro and in vivo. Vinblastine, midostaurin, and anlotinib as the representative of indole alkaloids, synthetic dimers and hybrids respectively, have already been clinically applied to treat many types of cancers, demonstrating indole alkaloids, synthetic dimers and hybrids are useful scaffolds for the development of novel anticancer agents. Covering articles published between 2010 and 2020, this review emphasizes the recent development of indole alkaloids, synthetic dimers and hybrids with potential in vivo therapeutic application for cancers.

Indole/isatin-containing hybrids as potential antibacterial agents.

The emergence and worldwide spread of drug-resistant bacteria have already posed a serious threat to human life, creating the urgent need to develop potent and novel antibacterial drug candidates with high efficacy. Indole and isatin (indole-2,3-dione) present a wide structural and mechanistic diversity, so their derivatives possess various pharmacological properties and occupy a salient place in the development of new drugs. Indole/isatin-containing hybrids, which demonstrate a promising activity against a panel of clinically important Gram-positive and Gram-negative bacteria, are privileged scaffolds for the discovery of novel antibacterial candidates. This review, covering articles published between January 2015 and May 2020, focuses on the development and structure-activity relationship (SAR) of indole/isatin-containing hybrids with potential application for fighting bacterial infections, to facilitate further rational design of novel drug candidates.