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UNIVERSITY OF MANAGEMENT AND
TECHNOLOGY
Submitted To: Dr Sohail Nadeem
Submitted By: Humaira Shaheen
Student ID: S2020140043
Section A
Case Study: Anticancer Activity of Alkynylgold (I) with P
(NMe
2
)
3
Phosphane
Department of Chemistry
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Anticancer Activity of Alkynylgold (I) with P (NMe2)3 Phosphane
Abstracts:
Alkynylgold (I) complexes
with hexamethylphosphorous
triamide P (NMe
2
)
3
(HMPT)
phosphane can be estimated by
using X-ray. The study of
complexes having R=4-OMe,
4- Br, their physicochemical
properties, antiproliferative
activity also characterized.
These complexes show optimal
balance of the hydrophilicity and lipophilicity because of water solubility of
hexamethylphosphorous triamide (HMPT). These complexes stable with physiological
condition' interact with transport protein and show greater anticancer activity in contradiction
of Caco-2 cell as compared to cisplatin. These complexes are batter candidate to use in
chemotherapy. some complexes do not show anticancer activity compared to enterocyte such
as differentiated cells and induced cell death by apoptosis, by the exposed of phosphatidylserine
(PS). The complexes which having halogens capture the cells in G2/M phase. Five of the total
complexes are better candidates, which are used in the chemotherapy.
Keywords: anticancer, Alkynylgold (I), hexamethylphosphorous triamide (HMPT),
phosphatidylserine, Chemotherapy
Introduction:
Colorectal cancer is the most ordinarily identified cancer after lungs and the breast cancer. The
maximum source of cancer death is liver, stomach and lung cancer. Drug is not accomplished
of fighting against cancer there by the aforementioned, in clinical exercise. Still there is not a
drug accomplished against cancer according to these standards by itself. Chemotherapy with
agents like oxalilplatin in mixture with leucovorin (LV) and with fluorouracil (FU) in stage III
is the standard of care for the cancer of colon. But this treatment is quiet controversial in stage
II patients (Abas et al. 2019). Chemotherapy, which based on platinum medicines, has been
troubled by a decrease due to sensitivity of these complexes. To overwhelmed this type of
disadvantages new investigates have motivated to new molecules to escape the progress of this
fight by altering the action of mechanism. Complexes of Ruthenium like RAPTA-C and
NAMI-A offerings an incredible cytotoxic activity. Nevertheless, other metals such as copper,
osmium, palladium and the gold are also being considering because of their auspicious
antiproliferative characteristics (Ferlay et al. 2015). Compounds of gold have extensive and
significant belief in medication; conversely, the real necessity to accomplish an active antitoxic
drug makes gold scientists to cultivate the new stable complexes of gold. Gold is biologically
applicable only with +1 and +3 t oxidative states. Gold(I) is the soft cation for soft ligands and
because of this gold(I) chemistry is built on phosphane ligands. Auranofin a gold complex is
known to prevent the increase of different cancer cells in vitro, but in vivo experimentations
were not consequently effective. The nature of the ligand which is existing in the complex will
interrupt the compound lipophilicity. The scheme of this complex stimulated the inquiry of
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gold (I) with hexamethylphosphorous triamide phosphane because of its higher water
solubility. In count to the gold and phosphorous bond it is decided that the coordination sphere
of gold saturate with changed aromatic groups. We nominated the phosphane in order to
distributed in well manner in organism. Alkynyl gold (I) examined because of their best
anticancer effect of gold (I) alkynyl with HMPT phosphane complexes on more than a few
tumour cell lines. Selenocysteine dependent enzymes for example thioredoxin reductase
(TrxR) is foremost target for gold complexes. New anticancer drugs development the
thioredoxin scheme is a suitable target (Tournigand et al. 2012).
Result and discussuon:
The current results indicated the breast cancer tissue showed a suggestively higher level of 8-
OHdG as compared to non-cancerous breast tissue. This result may support the hypothesis that
there is a higher risk of oxidative stress than non-tumour tissues neighbouring to cancer cells.
These results are different from earlier which Nagashima et al reported. By the HPLC-ECD
method who informed no numerical change of 8-OHdG levels in DNA between non-cancerous
breast and breast cancer tissues (Katano et al. 2002). As compared to the normal breast tissues
the breast cancer tissues accomudate greater level of 8-OHdG according to Mussarat et al.
Although paired specimens did not differentiate by Malins and Musarrat. Validation of human
intestinal Caco-2 cell line is auxiliary modal of small intestinal epithelium. Clonal origin that
originate from parental Caco-2 cell line used in different experiment and applications. Overall
cancers death the breast cancer is grades as the fifth cause of death that cause of cancers death
most probably in woman. After lung cancer, the breast cancer is the second major cause in
developing region after lung cancer (Mishima et al. 2002).
Synthesis and characterization:
Now the important point is the procedure of the synthesis of the compound named
AuCl(HMPT) so the new procedure is introduced that is better than the old method. An argon
atmosphere provided for the reaction because in this reaction we use HMPT that is sensitive
to the oxygen that is present in air, so we could get oxidized phosphane from this reaction. In
this reaction the sensibility
can be disappears when the
gold center is attached to the
HMPT. So, when we get the
starting point one of this
reaction the ligand
tetrahydrothisophene (tht) is
attached with HMPT. The
complex 1 can easily
converted into the either
alkynyl derivativs. This can be
done in the solution of the ethanol that can be never reported previously, So we can get the
scheme 1 which is shown in the figure. All the complex can easily soluble in the organic
solvents and stable at the room temperature. Ligands in the all complexes are in
deprotonated form shown by spectra of IR and 1HNMR and attached to the center of metal.
Due to the vibration of Au-CI stretching, it give the low frequency region. In addition, show
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