Despite major strides in reducing Plasmodium falciparum infections, this parasite still accounts for roughly half a million annual deaths. This problem is compounded by the decreased efficacy of artemisinin combination therapies. Therefore, the development and optimisation of novel antimalarial chemotypes is critical. In this study, we describe our strategic approach to optimise a class of previously reported antimalarials, resulting in the discovery of 1-(5-chloro-1H-indol-3-yl)-2-[(4-cyanophenyl)thio]ethanone (13) and 1-(5-chloro-1H-indol-3-yl)-2-[(4-nitrophenyl)thio]ethanone (14), whose activity was equipotent to that of chloroquine against the P. falciparum 3D7 strain. Furthermore, these compounds were found to be nontoxic to HeLa cells as well as being non-haemolytic to uninfected red blood cells. Intriguingly, several of our most promising compounds were found to be less active against the isogenic NF54 strain, highlighting possible issues with long-term dependability of malarial strains. Finally compound 14 displayed similar activity against both the NF54 and K1 strains, suggesting that it inhibits a pathway that is uncompromised by K1 resistance.

Distilled from the heartwood of Santalum album, Indian sandalwood oil is an essential oil that historically has been used as a natural active ingredient in cosmetics to condition and brighten the skin. It has been documented to exhibit antioxidant, anti-inflammatory, and anti-proliferative activities. Here, we investigated the protective and anti-aging effects of Indian sandalwood oil in scavenging reactive oxygen species (ROS) in HaCaT cells and in human skin explants after exposure to oxidative stress. Using a probe DCFH-DA, the antioxidant capacity of Indian sandalwood oil was monitored following exposure to blue light at 412 nm and 450 nm or cigarette smoke. The anti-aging effect of sandalwood oil was also explored in human skin explants via the assessment of collagenase level (MMP-1). We reported that Indian sandalwood oil possessed antioxidant potential that can scavenge the ROS generated by a free radical generating compound (AAPH). Subsequent exposure to environmental stressors revealed that Indian sandalwood oil possessed superior antioxidant activity in comparison to vitamin E (alpha tocopherol). Using human skin explants, this study demonstrated that Indian sandalwood oil can also inhibit the pollutant-induced level of MMP-1. The findings indicated that Indian sandalwood oil can potentially serve as a protective and anti-aging active ingredient in cosmetics and dermatology against environmental stressors.

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