the HIV protease inhibitors lopinavir/ritonavir, which were clinically evaluated for

potential treatment of human papilloma virus (HPV)-related preinvasive cervical

malignancies (Hampson et al., 2016), also showed potential for repurposing.

3.7

Potential Drugs for Repurposing Against Infectious Agents

3.7.1

Anticancer Drugs Repurposed Against Bacteria and Fungi

The drugs used against cancer have also been demonstrated to exhibit antibacterial

activity, particularly against gram-positive pathogens (Soo et al., 2016). Floxuridine

and streptozotocin, FDA-approved drugs used in colorectal cancer treatment and

pancreatic islet cell cancer, have exhibited activity against S. aureus by causing the

inhibition of SaeRS two-component system (TCS) (Yeo et al., 2018). Besides

causing significant changes in the transcription of S. aureus genes, these drugs

also inhibited the transcription of other virulence regulatory systems of S. aureus

(Yeo et al., 2018). Clofazimine (CZM), a drug used for the treatment of leprosy, was

repurposed for use against MDR-TB.

3.7.2

Immunomodulatory Drugs Repurposed Against Bacteria

and Fungi

Several anti-inflammatory and immunomodulatory drugs have also demonstrated

comparatively higher antibacterial activity against gram-positive as compared to

gram-negative bacteria and fungi. Celecoxib is a nonsteroidal anti-inflammatory

drug (NSAID) showing antibacterial activity by causing the inhibition of DNA

and RNA replication, protein synthesis, and cell wall formation while simulta-

neously reducing the levels of IL-6, TNF-α, IL-1β, and MCP-1 (monocyte

chemoattractant protein-1) against various pathogens, including S. aureus, Bacillus

anthracis, B. subtilis, and M. smegmatis. With the exception of linezolid, celecoxib

has demonstrated synergistic effects with several topical and systemic antimicrobials

used against S. aureus (Thangamani et al., 2015). Also, antidiabetic drug metformin

(MET) was reported to inhibit the intracellular growth of mycobacteria (Singhal

et al., 2014).

3.8

Concluding Remarks

The repositioning of drugs for a therapeutic indication besides the one originally

associated with their marketing is an upward trend these days. The foremost

objective of drug repurposing is to fight against the attrition and high costs that

have a dramatic effect on the number of new drugs that are entering the pharmaceu-

tical market, although this approach must be an add-on rather than being an alterna-

tive to the quest for the search of novel drugs.

32

A. Sharma and J. Kaur