Design and synthesis of highly oxygenated furo[3,2-c]pyran-4-ones and furo[3,2- c]chromen-4-ones scaffold as potential anticancer and antimicrobial agent

Synthesis of a number of highly oxygenated furo[3,2-c]pyran-4-one (4, 5) and furo[3,2c]chromen-4-one (8, 9) has been accomplished by a simple one pot reaction from easily available versatile starting materials dehydroacetic acid and 3-acetyl-4-hydroxycoumarin. All the synthesized molecules were characterized utilizing various spectroscopic techniques and screened for anticancer activity (in vitro) against three Colon (HCT-116, SW-620, HT24), Lung (A-549), Prostate-(PC-3), Breast-(MCF-7) cell lines. Compounds 5a, 9d, 9f showed good activity against breast MCF-7 cancer cell line having IC50 values 6.9, 2.8, 5.3 μM, respectively. Out of these compound 9d showed better activity against prostate PC-3 cell line with IC50 value 3.8 μM. The synthesized compounds were also studied for potential antibacterial activity (in vitro) using different strains of bacteria (Bacillus subtilis and Staphylococcus aureus -Gram-positive, and Escherichia coliGram negative) as well as fungal strains (Aspergillus niger and Candida albicans) using Norfloxacin and Fluconazole as antibacterial and antifungal standard drugs, respectively. The outcome of the antimicrobial screening study showed that compound 9f exhibited promising activity against S. aureus and B. subtilis while 5h showed excellent and 5i and 9b showed better activity against E. coli. The compounds 5c-5e displayed excellent activity against C. albicans and A. niger than Fluconazole.


Introduction
The development of innovative anticancer remedies with minimum toxicity and considerable activity is continuously explored area of anticancer research and among these, naturally derived agents grew substantial consideration because of their appreciable antitumor activity.

Chemistry
The designing of highly oxygenated furo [3,2-  In a similar manner, 3-acetyl-4-hydroxycoumarin and its chalcone were reacted separately with ɑ-bromoketones to obtain the desired products (8a-8c, 9a-9f) in acetonitrile under reflux in presence of potassium carbonate in excellent yield (Fig.4). All the products were characterized by IR, NMR (1H & 13C) and mass spectral data interpretation. The compounds 4c and 9a exhibited two moderate absorption bands. In compound 4c the band at 1746 cm -1 was due to stretching vibrations of lactone carbonyl group and the band at 1629 cm -1 was due to aroyl carbonyl group while in compound 9a, the band at 1753 cm -1 was due to stretching vibrations of lactone carbonyl group and the band at 1600 cm -1 was due to aroyl carbonyl group. 8 In 1 H NMR spectrum, compound 4c showed one singlet at δ 3.90 ppm due to methoxy group of at position-4 of aroyl ring and one doublet at δ 6.43 ppm due to 1H of pyran-4-one and phenyl ring protons displayed doublet having J value 6.88 Hz at δ 7.99 and 6.99 ppm due to 2'-H/6'-H and 3'-H/5'-H, respectively. In 13 C NMR spectrum, the peak at 182.41 ppm was assigned to carbonyl carbon and at 95.61 ppm was due pyran-4-one carbon and methoxy  The compound 9a showed two singlet at δ 3.81, 3.88 ppm due to methoxy group of styryl group and one singlet at δ 6.85 ppm due to 2H and one singlet at δ 7.17 ppm due to 1H  hydrogen-hydrogen correlation was observed in coumarin H9 with H8, H8 with H7, and H7 with H6 and aroyl hydrogens H2'/H6' with H3'/H5' and H6' with α proton and H3'/H5' with H4'.
Paclitaxel was taken as positive control. Results are summarized in Table 2. On analysis of results from the Table 2 Table 4.

Antifungal Activity
All the newly synthesized furo

Structure-activity relationship
The following structure-activity relationships were established from the antimicrobial and

Materials and Methods
Melting points are uncorrected and dignified in uncluttered capillaries. NMR spectrometer (Bruker Avance III) is used for 1 H and 13 C NMR spectra in CDCl3 where TMS is used for an internal standard solvent. Chemical shifts values are represented in ppm (parts per million).

Supporting Information
Supporting Information File 1: Experimental and cytotoxicity and antimicrobial assay details, compound characterization and NMR spectra.

Conflicts of Interest
The authors state that they have no conflict of interests.