Phenylahistin is a
metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
produced by the fungus ''
Aspergillus ustus'' that belongs to a class of naturally occurring
2,5-diketopiperazines featuring a dehydrohistidine residue that exhibit important biological activities, such as anti-cancer or neurotoxic effects.
Phenylahistin is a
microtubule
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...
binding agent that exhibits cytotoxic activities against a wide variety of tumor cell lines. A series of synthetic
analogs
Analog or analogue may refer to:
Computing and electronics
* Analog signal, in which information is encoded in a continuous variable
** Analog device, an apparatus that operates on analog signals
*** Analog electronics, circuits which use analog ...
were prepared to remove the
chirality
Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object.
An object or a system is ''chiral'' if it is distinguishable from ...
and optimize
biological activity
In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or ...
. These studies led to the potent anti-tumor agent
plinabulin
Plinabulin (provisional name BPI-2358, formerly NPI-2358) is a small molecule under development by BeyondSpring Pharmaceuticals, and is in a world-wide Phase 3 clinical trial for non-small cell lung cancer. Plinabulin is being investigated for th ...
, which is active in
multidrug-resistant
Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are c ...
(MDR) tumor cell lines.
References
{{Reflist
Diketopiperazines
Imidazoles