Synthesis of new curcuminoidesand studies of antitumor properties

Other Title(s)

تحضير مركبات كركمين جديدة و دراسة خصائصها ضد الأورام السرطانية

Dissertant

al-Salim, Tahsin Abd al-Qadir Abd al-Muhsin

Thesis advisor

Said, Bahjat Ali

Comitee Members

Salman, Usamah A.
Shihad al-Din, Nizar L.
Ilyas, Rita S.
Majid, Nisrin N.
al-Shaybani, Iqbal S.

University

University of Basrah

Faculty

College of Education for Pure Sciences

Department

Department of Chemistry

University Country

Iraq

Degree

Ph.D.

Degree Date

2013

English Abstract

The present work describes the synthesis, characterization and reactions of some new curcuminoids.

The practical chapter describes the preparation methods, for 28 compounds within three series.

Series (A) which includes symmetric curcuminoids that are prepared from the reaction of one mole of acetyl acetone and two moles of para alkyl or alkoxy benzaldehydes.

Series (B) includes chloro curcuminoids.

prepared from 3- chloro acetyl acetone and various substituted benzaldehydes.

The third series (C) includes asymmetric curcuminoids.

The first series contains 11 compounds five of them are para alkyl curcuminoids and five are para alkoxy and compound eleven All of these compounds were characterized by FTIR , EI- mass, ESI- ms and NMR spectra.

The EI mass spectra showed that all compounds exhibited parent peaks and base peaks The base peak for all alkyl curcuminoids (1-5) is due to the ion 69 [C4H5O+] , while the base peak in all alkoxy curcuminoids (6 -10) is due to the ion 147 [C10H11O+].

Electrospray ionization (ESI-Ms) was used to identify the compounds.

The molecular weights resulting from the ESI are found to match the calculated molecular weights, since the protonated ion of the analyst (M+H)+ can normally be used to determine the molecular weight of the compound.

Curcuminoids may exist as tautomeric mixture keto-enol forms, the IR spectra are characterized by medium bands corresponding to the stretching vibration of the carbonyl group which occur within the range 1626 - 1620 cm-1.

The NMR spectra for series A were recorded by using CDCl3 as a solvent.

In general, the spectra were identical and characterized by a one proton integral at 5.82pm which is attributed to the vinylic proton as well as the olifinic and aromatic protons appear within the range between (6.49- 7.67) ppm.

The 13C NMR spectra were characterized by four types of signals, aliphatic carbons signals, aromatic carbons signals, signals of olifinic carbon and signals of carbonyl carbon at 183.3ppm.

The dynamic 1H NMR of compound 2 was recorded between -50 to 30o C using CDCl3 as a solvent in order to follow the chelated proton in the enolic forms.

Both the chemical shift and the width of the signal changed with temperature.

The shape of signal changed from broad to sharp when going from15.94 to 16.31ppm.

Compound 11 was characterized by ESI-Ms , 1H NMR , IR and electronic spectra .

Series B included 9 compounds prepared according to the following scheme.

The proposed structures of the compounds were confirmed by various spectroscopic techniques including, HRMS (ESI), FTIR and 1HNMR.

The molecular weights predicted from the ESI were found to match the calculated molecular weights of curcuminoids.

The 1H NMR spectra of chloro curcuminoids (recorded using DMSO-d6) showed signals that match with curcumine signals with minor differences in some cases.

Due to the tautomeric forms are present in the solution of the compounds therefore signal of the –CH2- central group absent in the spectra of Series B , including that curcuminoid exists predominately as keto-enol tautomers in solution.

Dynamic NMR for compound Cl-1 was recorded between 30 to -40o C.

Compound Cl-1 was highly susceptible to pH at 7.2 and 9.1.

The hydrolysis of Cl-1 increased with time and degrades within 24 h pH 7.2 and pH 9.1 the solution change from yellow to colorless, giving ferulic acid, feruloylmethane and vanillin.

The asymmetric curcuminoids (series C) were prepared by using two different aldehydes with acetyl acetone.

The proposed structures of the compounds were confirmed by various spectroscopic techniques including, HRMS (ESI), FTIR and 1H NMR.

The 1H NMR spectra of asymmetric compounds show several signals, due to, the difference of the flanking groups at the sides of the chelating ring The anti-tumor activity of twenty of the studied compounds was examined against to two types of tumor cells which are PC-3 (prostate cancer) and T24 (bladder cancer).

Only five showed activity with cell growth inhibition between 89.8-50.6% against T24 and between 94.8 -72.8% against PC3.

The IC50 for the synthesized curcuminoids between 30.5 and 22.16 μmol at 24h, Cl-6 has higher activity against PC-3 and T24 than other curcuminoids .

The molecular structure of Compound 8 was determined by using single crystal X-ray diffraction.

The unit cell packing consists of eight molecules arranged to give monoclinic crystal system of dimensions (a ≠ b ≠ c, α = γ= 90°, β ≠ 90°).

From the crystal structure the chelating ring is not symmetric, since the two C-O distances as well as the distances C8-C16 and C8-C12 being significantly different.

Compound 8 had been theoretically investigated using the DFT method, at the B3LYP level of theory along with standard 6-31G(d) basis set.

The Gaussian 09 package was employed to perform optimization of structures and all the calculations.

The correlation IR data of practical and theoretical showed the same frequency.

Main Subjects

Chemistry

No. of Pages

186

Table of Contents

• APA
• MLA
• AMA

Language

English

Data Type

Arab Theses

Record ID

BIM-744071