3'-Chloropropiophenone is a chiral compound that is used as an antidepressant drug. It was first synthesized in the 1950s and has been studied extensively for its pharmacological effects. It is a racemic mixture of two enantiomers, one of which is active and the other inactive. The active enantiomer binds to serotonin receptors and inhibits the reuptake of serotonin, which leads to an increase in serotonin levels. The inactive enantiomer does not bind to serotonin receptors and does not inhibit the reuptake of serotonin. 3'-Chloropropiophenone has been shown to be effective when administered at an optimum concentration of 5 milligrams per kilogram body weight.

Enhanced whole-cell biotransformation of 3’-Chloropropiophenone

Halogenated organic compounds include vinyl chloride, carbon tetrachloride, methylene chloride, polychlorinated biphenyls, 3’-Chloropropiophenone, and many more. Some of these compounds are important precursors or intermediates in the synthesis of pharmaceuticals, agrochemicals, flavors, and functional materials One such halogenated organic compound is 3’-Chloropropiophenone which upon hydrogenation, may be transformed into 3-chloro-1-phenylpropanol which is essential for preparing antidepressants like (S)-fluoxetine, nisoxetine, and (R)-tomoxetine. The whole-cell biocatalytic system might be used either as free cells or immobilized (entrapped) ones under optimized conditions. Aquasorb is a water retainer that, when absorbs water, becomes hydrogel. Upon incorporation into soil or water, it is capable of absorbing and retaining up to 500 times more water and nutrients than its dry weight. Due to the efficient water absorption-release cycle of Aquasorb, we have utilized it for whole-cell entrapment of C. emersonii (211.8b) for the first time and its biocompatibility was assessed. We have also studied and compared the biotransformation (dehalogenation) efficiency of both free and entrapped C. emersonii (211.8b) cells for halogenated organic substrate (3’-Chloropropiophenone).[1]

An equivalent volume of culture (150 mL each) for both free and hydrogel entrapped cells of C. emersonii (211.8b) were prepared in 500 mL flasks having an OD750 value of 1. To find out the suitable concentration of the substrate which can be tolerated by both free and entrapped cells, different concentrations of 3’-Chloropropiophenone (0, 2, 5, and 10 mM) were added directly to the cultures. To determine the biotransformation capacities of both free and entrapped microalgae for halogenated organic substrate, the optimal concentration (5 mM) of 3-CPP was added to both the cultures. A promising number of entrapped cells was achieved in terms of colony-forming units (CFUs?=?2.1?×?104) per hydrogel bead with a comparable growth pattern to that of free cells. It was determined that there is no activity of hydrogenase that could transform 1-phenyl-2-propenone into 1-phenyl-1-propanone because after 12 h the ratio between two products (0.36?±?0.02) remained constant throughout. Furthermore, it was found that the entrapped cells have higher biotransformation of 3’-Chloropropiophenone to 1-phenyl-1-propanone as compared to free cells at every interval of time. A halogenated organic substrate (3’-Chloropropiophenone) was biotransformed using both free and hydrogel entrapped microalgae C. emersonii (211.8b) as biocatalyst. Besides, significantly higher biocatalysis of 3-CPP was observed in treatment with entrapped cells. No activity of hydrogenase was found that could transform 1-phenyl-2-propenone into 1-phenyl-1-propanone because of the ratio between 1-phenyl-1-propanone/1-phenyl-2-propenone remained constant after 12 h.

New GABA modulators protect photoreceptor cells

No clinically approved therapies are currently available that prevent the onset of photoreceptor death in retinal degeneration. Signaling between retinal neurons is regulated by the release and uptake of neurotransmitters, wherein GABA is the main inhibitory neurotransmitter. In this work, novel 3'-Chloropropiophenone derivatives and the clinical anticonvulsants tiagabine and vigabatrin were tested to modulate GABA signaling and protect against light-induced retinal degeneration. GABA modulatory drugs are clinically available as anticonvulsants. In patients with epilepsy, overexcitation of neurons causes seizures, which are controlled pharmacologically by decreasing excitatory signaling and increasing inhibitory signaling.[2]

In this work, GABA modulatory compounds were evaluated for prevention of photoreceptor loss in mouse models of light-induced retinal degeneration. Clinical anticonvulsants and novel 3'-Chloropropiophenone derivatives provided structural and functional protection of the retina in a light-sensitive Abca4?/?Rdh8?/? mouse model of retinal degeneration. Moreover, the chloride derivatives demonstrated a safe profile and effective protection against light-induced retinal degeneration in wild-type BALB/c mice. 3'-Chloropropiophenone derivatives, a new class of GABA-AT inhibitors, effectively protected retinal structure and function in Abca4?/?Rdh8?/? mice that were treated before exposure to intense light. Clinical anticonvulsants that act on the GABA shunt were also shown to provide retinal protection in this model. Furthermore, the lead chloride derivative CL-4 replicated this protective effect in wild-type BALB/c mice.

References

[1]Khan, Sikandar et al. “Enhanced whole-cell biotransformation of 3-chloropropiophenone into 1-phenyl-1-propanone by hydrogel entrapped Chlorella emersonii (211.8b).” Biotechnology letters vol. 43,12 (2021): 2259-2272. doi:10.1007/s10529-021-03194-y

[2]Schur, Rebecca M et al. “New GABA modulators protect photoreceptor cells from light-induced degeneration in mouse models.” FASEB journal : official publication of the Federation of American Societies for Experimental Biology vol. 32,6 (2018): 3289-3300. doi:10.1096/fj.201701250R