Cytochrome bd (cyt-bd) oxidase, one of the two terminal oxidases in the Mycobacterium tuberculosis (Mtb) oxidative phosphorylation pathway, plays an indispensable role in maintaining the functionality of the metabolic pathway under stressful conditions.
Hypoxia is a condition caused by a decrease in oxygen and is often seen in cases of cardiac ischemia, solid tumors, inflammation, and other diseases. Tumor hypoxia can result in cancer invasion, metastasis, decreased apoptosis, and resistance to various therapies (chemotherapy, immunotherapy, and radiotherapy), ultimately reducing overall survival rates. These effects of hypoxia underline the need to monitor hypoxia‐associated specific markers for more effective therapeutic intervention. Nitroreductase (NTR) is a common biomarker of hypoxia, via its reduction activity with nitroaromatic compounds to corresponding amino derivatives using NADH and NADPH as cofactor. The NTR expression level can be correlated to cellular hypoxia. Therefore, developing a diagnostic tool for measuring NTR activity is of immense importance for improving treatment efficacies. To leverage NTR activity as a proxy of hypoxia, small molecule based fluorescent probes have been developed as quantifiable probes. To date, several NTR‐sensitive fluorescent probes have been reported. This review is focuses on the advances in these fluorescent NTR probes over the last five years.
Leishmaniasis, one of the neglected diseases, ranks second to malaria in the cause of parasitic mortality and morbidity. The present chemotherapeutic regimen faces the limitations of drug resistance and toxicity concerns, raising a great need to develop new chemotherapeutic leads that are orally administrable, potent, non-toxic, and cost-effective. Several research groups came forward to fill this therapeutic gap with new classes of active compounds against leishmaniasis, one such being 3,3′-diindolylmethane (DIM) derivatives. We tried to link this concept with another promising approach of glycoconjugation to study how glycosylated groups work differently from non-glycosylated ones. In the present study, a series of 3,3′-DIM derivatives have been synthesized and screened for their anti-leishmanial potency on Leishmania donovani promastigotes. Next, we synthesized the β-N,N′ glycoside of potent compound 3d using indole–indoline conversion, Fischer-type glycosylation, 2,3-dichloro-5,6-dicyano-1,4-benzoquionone (DDQ) oxidation, and molecular iodine catalyzed coupling with a suitable aldehyde in reasonable overall yield. The biological evaluation revealed that glycosides had reduced cytotoxic effects on the J774A.1 macrophage cell line. The enzyme inhibition study confirms that the glycoside derivatives have significant inhibitory activity against the leishmanial topoisomerase IB enzyme. Molecular docking further displayed the better binding efficiency of glycoside 13 with the target enzyme, suggesting the involvement of more H-bond interactions in the case of glycosides as compared to free drugs. Therefore, this work helps in proposing the fact that the addition of sugar moieties adds some favorable characteristics to free inhibitors, making it a promising approach for future clinical diagnostic and therapeutic applications, which can prove to be a valuable arsenal in combating such neglected diseases.