Small molecules as activators in medicinal chemistry (2000–2016)

ABSTRACT

Introduction: From therapeutic point of view, it is often beneficial to enhance the expression of certain enzymes whose low expression is responsible for the observed ailment. Small molecules as activators of several enzymes have great biological potential as anti-microbial and anti-cancer agents, for the treatment of diabetes, obesity, metabolic disorders, and for the treatment of neurological disorders including Alzheimer’s disease. This review covers patents describing small molecules as activators, and provides structural leads for the design of even more potent activators.

Area covered: This review is focused on small molecules that have been explored as activators of enzymes in the last and current decade (2000–2016).

Expert opinion: The ability to modulate activity of enzymes has long been a quest of medicinal chemistry. This has been the impetus behind the development of a plethora of drugs as enzyme inhibitors. However only a few enzyme activators as drugs have made it to the market. Disorders characterized by supressed enzyme activity can be treated by enhancing the activity of a specific enzyme.

KEYWORDS:

• Small molecules
• enzymes
• activators
• bacterial infections
• cancer
• Alzheimer’s disease

Article highlights

• The ability to modulate expression and activity of physiologically relevant biological targets has long been a pursuit of medicinal chemistry. This has been the driving force behind the design and development of a plethora of drugs as enzyme inhibitors. In a similar way, many small molecule activators are also known that increase the expression of specific enzymes.

• The combined knowledge of small molecule inhibitors as well as activators of specific biological targets, such as enzymes, aids the human ability to fine-tune the desired expression of these biological targets with great therapeutic implications.

• Synthetically accessible, small molecule activators are also advantageous due to their potential to act as probes to investigate the physiological effects of selectively increasing the expression of a specific target/enzyme.

• This review covers small molecules patented (from 2000-2016) as activators of therapeutically important biological targets and enzymes with potential to be used as antimicrobials, ion channel openers, anti-Alzheimer’s, anti-diabetic treatment, anticancer and anti-epileptic agents.

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Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

Higher Education Commission (HEC) Pakistan (Project Number 20-1910) is gratefully acknowledged for financial support.