Therapeutic delivery of siRNA for the management of breast cancer and triple-negative breast cancer.

Breast cancer is the leading cause of cancer-related deaths among women globally. The difficulties with anticancer medications, such as ineffective targeting, larger doses, toxicity to healthy cells and side effects, have prompted attention to alternate approaches to address these difficulties. RNA interference by small interfering RNA (siRNA) is one such tactic.

Design and synthesis of non-hydroxamate lipophilic inhibitors of 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR): , and antibacterial studies.

1-Deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) is a key enzyme of the 2--methyl-d-erythritol 4-phosphate (MEP) pathway operating in several pathogens, including and . Since a DXR homologue is not present in humans, it is an important antimicrobial target. Fosmidomycin (FSM) and its analogues inhibit DXR function by chelating the divalent metal (Mn or Mg) in its active site a hydroxamate metal binding group (MBG).

Crystal structures of non-uracil ring fragments in complex with Mycobacterium tuberculosis uracil DNA glycosylase (MtUng) as a starting point for novel inhibitor design: A case study with the barbituric acid fragment.

Uracil DNA glycosylase (UDG or Ung) is a key enzyme involved in uracil excision from the DNA as a repair mechanism. Designing Ung inhibitors is thus a promising strategy to treat different cancers and infectious diseases. The uracil ring and its derivatives have been shown to inhibit Mycobacterium tuberculosis Ung (MtUng), resulting from specific and strong binding with the uracil-binding pocket (UBP).

Identification of a new and diverse set of Mycobacterium tuberculosis uracil-DNA glycosylase (MtUng) inhibitors using structure-based virtual screening: Experimental validation and molecular dynamics studies.

Mycobacterium tuberculosis uracil-DNA glycosylase (MtUng), a key DNA repair enzyme, represents an attractive target for the design of new antimycobacterial agents. However, only a limited number of weak MtUng inhibitors are reported, primarily based on the uracil ring, and hence, lack diversity. We report the first structure-based virtual screening (SBVS) using three separate libraries consisting of uracil and non-uracil small molecules, together with the FDA-approved drugs.

Non-hydroxamate inhibitors of 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR): A critical review and future perspective.

1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) catalyzes the second step of the non-mevalonate (or MEP) pathway that functions in several organisms and plants for the synthesis of isoprenoids. DXR is essential for the survival of multiple pathogenic bacteria/parasites, including those that cause tuberculosis and malaria in humans. DXR function is inhibited by fosmidomycin (1), a natural product, which forms a chelate with the active site divalent metal (Mg/Mn) through its hydroxamate metal-binding group (MBG).