Synthesis, Anti Cancer and Anti Fungal Studies of New Phenyl Ethylene Derivatives

Synthesis of Phenyl ethylene derivatives (4a-4f ) are reported in this communication. Products were characterized by 1 HNMR, Carbon ( 13 C) NMR and Mass spectral data. Synthesized compounds of 4a-4f were screened for anti cancer and anti fungal activities and their results are presented. The main intermediate (3) was prepared from 4-methoxy phenyl acetone (1) reacted with aqueous ethylamine and NaBH4 to get the compound (2).Further dehydrohalogenation of (2) with 4bromobutanol and potassium carbonate at 80°C resultedin compound (3)which on further dehydration with p-toluene sulfonic acid under reflux conditionsgave 4a to 4f.


INTRODUCTION
Phenyl ethylamine derivatives were found with very good biological activities viz., anticancer, antifungal. In addition some of the phenyl ethylamine derivatives also act as a musculotropic antispasmodic agent with a direct action on the smooth muscle of the gastrointestinal tract (GIT) especially phenyl ethyl amine derived esters are found to be inhibiting

Original Research Article
the peristaltic reflex of the guinea-Pigilem and inhibiting sphincter of odietc [1,2].
Besides the synthetic phenyl ethylamine and derivatives are also ofgreat value in our daily life. Keeping in view, the author focused on the synthesis of phenyl ethylene derivatives. These scaffolds and analogs are being subjected to biological screenings like antifungal and anti cancer activities.

MATERIALS AND METHODS
Preparation of phenyl ethylene derivatives from 4-methoxy phenyl acetone (1)

RESULTS AND DISCUSSION
The compounds are prepared by using the synthetic scheme shown below.The main intermediate (3) was prepared from 4-methoxy phenyl acetone (1) using reductive amination with aqueous ethylamine in the presence of Sodium borohydride to get the compound (2). Further dehydrohalogenation of (2) with 4bromobutanol and potassium carbonate at 80°C resulted compound (3) which on further dehydration with p-toluene sulfonic acid under reflux conditions gave 4a to 4f.Products are characterized by 1 HNMR , 13 C NMR and Mass spectral data [1][2][3][4].

MCF-7
MCF 7 is a human breast cancer cell line with estrogen, Progesterone and glucocorticoid receptors. It is useful for the in-vitro breast studies because they retained several ideal characteristics particular to mammary epithelium such as the processing of estrogen, in the form of Estradiol. It is the first human responding breast cancer cell line. It proves to be a suitable model cell line for breast cancer investigation worldwide. MCF 7 allows the researchers to use this cell line for bringing more light into breast cancer pathogenesis and treatment protocols through reliable in-vitro assay.

Hela cells
Refer to a line of cells belonging to a strain that has been continuously cultured since 1951. Compared to other human cells, Hela cell were the only survive in-vitro. Hela cells could be good acceptor for cross contamination with other cell line and possibility to lead number of misidentification cell line. Genome of Hela cell is highly unstable. In a lab setting hela cells was a first cell line that could be easily shared and multiplied.
Hele cell line was invented by Johns Hopkins. He is not expected any returns from the innovation of HeLa cells and he distributed HeLa cells to scientific research with free of cost. The very good contribution of Hela cell line in medical breakthrough. From research on the effects of zero gravity in outer space and the development of polio and COVID-19 vaccines, to the study of leukemia, the AIDS virus and cancer worldwide.

Antifungal Activity
Aspergillus candidus is a common contaminant of grain dust and causes respiratory disease in human. The species is widely distributed in nature and grows on vegetation in the later stages of decay. Aspergillus niger is fungi, it is also common contaminated foods grapes, apricots, onions, and peanuts. It cause a disease called Black mold. Aspergillus niger is less likely to cause human disease than some other Aspergillus species. In extremely rare instances, humans may become ill, but this is due to a serious lung disease.

Process for the preparation of title compounds 4(a-h)
Carried out the dehydration of compound 4 and corresponding acid in-presence of PTSA and toluene at 105 to 115 °C for 22+5 h. after maintenance cool the reaction mass and charge water into the reaction mass and stirr for 10 min and separated the organic layer and distilled the organic layer(toluene) completely. The obtained crude was purified with column chromatography by using 5-8 % of Dichloromethane in Ethyl acetate.  (1-(4-methoxyphenyl)

Anti Cancer Activity
Calculated IC 50 values of the anti Cancer activity of newly synthesized phenyl ethylene derivatives against MCF7 and HeLa cell line are tabulated in Table 1. All the compounds are found to be showing good anti cancer activity. Some of the compounds 4d, 4e, and 4f showed high potential and remaining compounds showed moderate potential values. All have shown the zone of inhibition but 4e has shown very high zone of inhibition to Aspergillus nigerand Aspergilluscandidus

Antifungal Activity
The antifungal activities with zone of inhibition of all the newly synthesized 2-phenyl ethylene derivatives were evaluated in vitro against a wide variety of fungal species such as Aspergillusniger and Aspergillus candidus. All the compounds exhibited antifungal activity less than the reference standard Pencillin G. compound 4a and 4e exhibited good antifungal activity than remaining compounds [5-8].

CONCLUSION
In the present study, we have reported the synthesis of 4-[Ethyl(4-methoxy-a-methyl phenethyl)amino]butyl veratrate and their novel derivatives were found to be broad spectrum anticancer and antifungal agents. Results suggest the utility of the these novel series against cancer and fungal diseases, Still some more studies are in progress to optimize these molecules to get the potent inhibitor, and will report in the due course.

CONSENT
It is not applicable.

ETHICAL APPROVAL
It is not applicable.