Curcumin:

When Hcur is treated with a base, the base takes the most acidic proton (from the carbon present between two carbonyl group also known as ‘Active Methylene Group’) and after deprotonating, the two oxygen atoms become chemically equivalent and capable of acting as ligand towards the hard metal ions [2]. Applying this concept, there is a very popular strategy to stabilize curcumin (deprotonated) i.e. to combine with a metal centre to make a suitable metal-ligand interaction to get a sufficiently stable system in an aqueous medium. This type of metal-based therapy is quite familiar from the 1980s and reminds us of the widely used potential anticancer drug cisplatin, oxaliplatin etc.

So now the metal has given us the platform to introduce curcumin in physiological environment with more lifespan. This is expected because now curcumin will be circulated as metal-bound form and will not readily get hydrolysed and during circulation, it will reach into the cancer cells .Based on above mentioned hypothesis thousands of metal (Ruthenium, vanadium, platinum etc)-curcumin based prodrug has been reported and control studies show that metalbased complex is far more therapeutically effective than free curcumin. Few of them are s h o w n below

Turmeric is one of the most used traditional spices in our kitchen that we come across every day. Not only as a spice but also from the ancient time it is being used in medicinal purposes such as antioxidant, antimicrobial, anti-inflammatory, skincare etc. But this decade has seen a totally new role of turmeric as a potential cytotoxic agent against cancer cells in the field of medicinal chemistry and pharmacy and this is due to Curcumin (Hcur), a naturally occurring polyphenolic active ingredient. Study reveals that Curcumin induces apoptosis in tumour cells by inhibiting the activity of the transcription factor NF-κB. [1]

Then the question comes, as curcumin is being derived from edible kitchen spice, there is no biosafety issue, so why don’t we prescribe cancer patients few grams of curcumin every day to get well soon? The answer lies within the chemical structure of curcumin. Due to the presence of a β-diketone moiety it is very much susceptible to hydrolysis. So the main disadvantage of this compound is its less bioavailability in physiological condition as it is highly unstable in aqueous medium. To overcome this difficulty, the role of the chemists comes into the picture.

Also, Hcur is very photosensitive and upon irradiation with visible light (400-700 nm) it generates Reactive Oxygen Species (ROS) which then creates cellular stress and can kill a cancer cell .[8] Treatment of cancer by this type of method is called Photo Dynamic Therapy (PDT), which is an emerging research area nowadays . There is another very popular strategy called Photo Activated Chemo Therapy (PACT),in which upon irradiation by the light the metal-ligand bond breaks and Hcur get released from the metal centre inside the cell

and act on its cellular target (NF-κB). The free metal centre then can also attack the nucleophilic centre of DNA or any other cellular protein to damage them and induce apoptosis.

Though the metal- based drugs are potential cytotoxic, but the main problem with them is their lack of selectivity towards the cancer cells. So, randomly they can also enter inside the normal body cells to cause massive side-effects by damaging the healthy body cells. As mentioned curcumin is a potential photoactive moiety, so after the treatment with metalcurcumin based prodrug, in a patient’s body only the cancer cells (though identifying them is challenging) will be exposed to photo irradiation and as a result the curcumin gets activated inside the cancer cells only and can work in PDT or PACT way. This is the specialty of curcumin based prodrug or any other photoactivable prodrug. This type of therapeutic strategy helps to reduce side-effects as there are no cytotoxic effects in the light unexposed healthy body cells i.e. even if the prodrug has entered inside them, due to absence of light it will not be converted into the active drug thereby minimizing the damage in healthy cells. One of the examples of photoactivable cytotoxicity of curcumin is shown below [8]-PDT and PACT are an emerging and promising method of therapy. Besides curcumin there are many other photosensitive anticancer agents are being reported and every single of them gives us the ray of hope to fight against 18.1 million cancer cases across the world(9.6 million deaths, in 2018, according to WHO).

REFERENCES

1)Avishek Jana, Brijesh K. Verma, Aditya Garai, Paturu Kondaiah, Akhil R. Chakravarty, Inorganica Chimica Acta, 2018, 483, 571.

2. Tukki Sarkar, Akhtar Hussain, Enz Eng., 2016, 5, 143.

3. Riccardo Pettinari, Fabio Marchetti, Francesca Condello et al,Organometallic, 2014, 33, 3709−3715

4. Utso Bhattacharyya, Brijesh Kumar, Aditya Garai, Arnab Bhattacharyya, Arun Kumar, Samya Banerjee, Paturu Kondaiah, Akhil R. Chakravarty, Inorg. Chem., 2017, 56, 12457

5. Md Kausar Raza, Koushambi Mitra, Abhijith Shettar,bUttara Basu, Paturu Kondaiah and Akhil R. Chakravarty, Dalton Trans., 2016, 45, 13234

6. D. E. J. G. J. Dolmans, D. Fukumura, R. K. Jain, Nat. Rev. Cancer, 2003, 3, 381−387

7. Sylvestre Bonnet, Dalton Trans., 2018, 47, 10330-10343

8. Tukki Sarkar, Akhtar Hussain, Enz Eng., 2016, 5, 143.