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Drug Design and Chemotherapy
Phramacy 

Drug Design and Chemotherapy | Sample Pharmacy Assignment

Mathews

Introduction

The design process of the drug is one of the major stages to develop a suitable treatment facility for cancer and associated disorders. Incorporation of suitable protease inhibitors as anti-cancer mechanisms within affected cells has been analyzed to develop a better strategy and cure cancer for tumour microenvironment. Comparison between different drug designing strategies has been done to find a reliable solution considering alternative approaches have been discussed.

Discussion

Relevant approaches to design protease inhibitors

In order to treat cancer and design anti-cancer activities, the involvement of the following approaches has been considered.

Nelfinavir and relevant protease inhibitors

Anticancer activities can be promoted within cells affected from cancer using Nelfinavir and other suitable protease inhibitors based approaches. PIs have been classified considering the anti-cancer mode for action and relevant pathway (nhs.uk, 2020). Endoplasmic reticulum stress unfolded protein response and adequate Akt inhibition have been used as two primary mechanisms under this approach. In order to support cancer treatment facility, the inclusion of MMP-9 and MMP-2 inhibition, different regulators, IGF, surviving, Fatty acid Synthase has been done within Nelfinavir approach of protease inhibitor development process. Decrease of invasion due to MMP2 and 9, misfolded protein accumulation and UPR that incorporate Autophagy support to design suitable drug-based solution to become an adequate reason for the death of the cell.

Figure 1: Approaches to design protease inhibitors

Figure 1: Approaches to design protease inhibitors

(Source: Srikanth and Chen, 2016, p. 470)

Plant Protease inhibitors

Biochemical and molecular genetics level exploration of plan protein and its relevance to design affordable protease inhibitors for treating cancer cells have been considered in this process. The protection system of plants against severe diseases, insects and other troubles can be utilized to accumulate adequate process for designing protease inhibitors to resist certain unwanted biological activities such as inflammations, blood clotting and other processes. In order to prevent cancer, Bowman-Birk inhibitors (BBI) have been considered effectively rather than other PIs (Srikanth and Chen, 2016, p. 470). Variation of concentration, heat stabilities have been observed to implement an adequate anti-cancer activity within a human cell. Hence, considering the therapeutic importance of plan based protease inhibitors drugs for cancer can be designed.

The molecular and biological basis

Physiological and pathological importance of protease inhibitors is considered under anti-cancer drug development based on a molecular and biological basis. Clinical approach to design adequate molecular and biological basis enabled the systematic design of drug helps to incorporate an affordable solution to selectively treat cancer cells. Suitable mechanism of stimulation technique ensures anti-cancer procedures based on radiotherapy and other intervention mechanisms (Roma-Rodrigues et al. 2019, p. 840). The structure-activity relationship has been studied in this approach to eliminate drawbacks of inhibitors and secure the chance of recovery against cancer.

Demonstrate a comparison between different drug designing strategies to treat cancer cells

Incorporation of drug designing strategies has been done to demonstrate comparative analysis between affordable solutions to treat cancer cells in the human body.

Chemotherapy

Consideration of one or multiple drugs to mitigate risks regarding cells affected by cancer has been done in the chemotherapy process. Combination of surgery, hormone therapy and radiation are used to treat serious cancer affect cells based on the stage and type of cancer. In this case, personal treatment preference and many more factors have been considered to design an efficient drug to act as anti-cancer (Janmaat et al. 2017, p. 21). Traditional drugs under chemotherapy treatment are cytotoxic to cells and affect in the normal condition. Therefore, healthy cells might get affected along with killing cancer cells within the human body.

Cancer treatment strategies

Figure 2: Cancer treatment strategies

(Source: Janmaat et al. 2017, p. 21)

Targeted therapy

In order to ensure the killing of cancer cells without harming or with lesser damage to normal cells, target therapy has been incorporated.

Deubiquitination process

Multidrug-resistant and associated proteins have been considered in this strategy for ensuring anti-cancer activity within human cells. Adequate proteasome system has been involved considering ubiquitin complex to develop this cancer therapy. Protease helps to remove ubiquitin chain from the target cells considering its molecular structure and frameworks.

Deubiquitination process

Figure 3: Deubiquitination process

(Source: Patel et al. 2018, p.2089)

On the other side, Marimastat can be considered to the patients who have seriously taken drugs and other factors of treatments. Integration of metalloprotease inhibitors based on broad spectrums of the matrix has been done to treat cancer in the metastatic stage (Patel et al. 2018, p.2089). Involvement of thermosensitive liposomes and many other factors have been considered to improve the existing situation of cancer affected cells. Substances are blocked within the tumour microenvironment and locked. In this regard, locked cells are destroyed concerning normal cells using the cytotoxic nano-medicine (Srikanth and Chen, 2016, p. 470).

Figure 4: Marimastat and Batimastat

(Source: Created by researcher)

AZT

Zidovudine group of medication process based on antiretroviral systematic approach have been considered in AZT (Glickman, and Sawyers, 2012, p. 17). This helps to reduce the proliferation of different cancers and initiates the apoptosis process. This strategy for drug develops is more often used for compound medication approach.

 

Figure 5: AZT

(Source: Created by researcher)

A reliable strategy to meet the biological target

Incorporation of metastatic treatment and suitable facilities has been ensured to enhance the percentage of recovery from cancer. Drug resistance is one of the key alarming threats to chemotherapy and relevant anti-cancer activity. Therefore, In order to reduce the harmful impacts of such drugs involvement of adequate target therapy can be done. Target therapy identifies too much protein in a cancer cell and change in the DNA structure of the cancer cell (Tan et al. 2018, p. 29). Incorporation following strategies has been done to treat cancer cells by target therapy technique:

  • Chemical signals are become discontinued to block the cell from mutation
  • Change in protein substances to kill the cancer cells
  • Provide restrictions to make new blood vessels (Glickman, and Sawyers, 2012, p. 17)
  • Enrich the immune system to reduce the number of cancer affected cell in the tumour microenvironment
  • Target cancer cells with toxins to kill those certainly

Alternative approaches to activate anticancer pro-drugs in tumour

In the modern prodrug treatment of cancer, gene direct enzyme is used that improve the therapeutic ratio in an intervention. According to previous observations in this study, it can be stated the presence of fusion protein cancer cells somehow influence each other and increase the number of cancer cells as well. The killing of cancer cells is enhanced with the prodrug ZD2767P than CPG2 in fused condition. This actually helps in destroying the biological binding site of the malignant cells. Thus, the approach of using this prodrug in tumour conditions is more effective. The chemical structure of this prodrug is depicted in the picture below –

Figure 6: ZD2767P (CJS149)

(Source: Created by Researcher)

This prodrug is developed mainly for three different reasons which are-

  • Analyzing the tumours that targeting of the antibody-enzyme conjugate
  • To study the new prodrug named bisiodophenol mustard
  • To mitigate the problems of long-acting activate drugs (ac.uk, 2020)

On the other hand, one of the practical approaches in chemotherapy is Palbociclib which worked as inhibitors like CDK4 and CDK6. Though, this prodrug is more effective in the case of breast cancer. Still not alone, a mixture of Palbociclib and letrozole work better in case of ER-positive and HER2-negative breast cancers. Again Ribociclib and Palbociclib are also used together in the treatment of breast cancer. The target site is called kinases biologically. For example, tyrosine kinase is a receptor which is mainly targeted by bispecific toxin conjugates (ncbi.nlm.nih.gov, 2020). The chemical structure of tyrosine is given below-

Figure 7: Tyrosine [Tyr (Y)]

(Source: Created by Researcher)

Though, in leukaemia, a particular type of tyrosine kinase is affected that named Bcr-Abl tyrosine kinase. Breast cancer is drug-resistant cancer, but in breast cancer treatment, Ribociclib impacted almost similarly as combined treatment with letrozole and Palbociclib. The chemical structures of these two prodrugs are shown in Figure 8 below.

Figure 8: Palbociclib and Ribociclib

(Source: Created by Researcher)

Apart from all of the approaches mentioned above, copolymers are also used as an anticancer agent in cancer treatment (Ma et al. 2016, p. 29). For example, the HPMA polymer is used where the prodrug named doxorubicin is attached to its back using Gly-Phe-Leu-Gly peptidyl string as a linker. The structure of HPMA with doxorubicin is shown in the next figure. Again, this drug also impacted on the biological target site and finished the tumour appropriately.

Figure 9: Chemical structure of HPMA polymer

(Source: Created by Researcher)

Conclusion

From the above discussion, it is clear that many different approaches are taken for cancer and tumour treatment. Though, it can be concluded that more or less, the methods of the treatments are quite the same. Most of the effective treatments are done using prodrugs and co-polymers. There are mainly two things that are common in the procedures. Firstly, all of the therapy attacked the binding site enzyme of the malignant cells. Secondly, the cancer cells developed resistant against the drugs and reduced the effectiveness of the medications on attacking the sites. Though, this can be overcome using site-specific chemotherapy that is done in the case of treatment with HPMA copolymer as well.

References

core.ac.uk, 2020, anticancer prodrug. Available at: https://core.ac.uk/download/pdf/287333375.pdf [Accessed on 2nd August 2020]

Glickman, M. S., and Sawyers, C. L. (2012). Converting cancer therapies into cures: lessons from infectious diseases. Cell, 148(6), 1089–1098. https://doi.org/10.1016/j.cell.2012.02.015

Janmaat, V. T., Steyerberg, E. W., van der Gaast, A., Mathijssen, R. H., Bruno, M. J., Peppelenbosch, M. P., Kuipers, E. J., and Spaander, M. C. (2017). Palliative chemotherapy and targeted therapies for esophageal and gastroesophageal junction cancer. The Cochrane database of systematic reviews, 11(11), CD004063. https://doi.org/10.1002/14651858.CD004063.pub4

Ma, L., Ma, R., Wang, Z., Yiu, S.M. and Zhu, G., 2016. Heterodinuclear Pt (iv)–Ru (ii) anticancer prodrugs to combat both drug resistance and tumor metastasis. Chemical Communications, 52(71), pp.10735-10738.

ncbi.nlm.nih.gov, 2020, prodrug application. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147050/ [Accessed on 31st July 2020]

nhs.uk, 2020. Radiotherapy. Available at: https://www.nhs.uk/conditions/radiotherapy/ [Accessed on 29th July 2020]

Patel, K., Ahmed, Z.S., Huang, X., Yang, Q., Ekinci, E., Neslund-Dudas, C.M., Mitra, B., Elnady, F.A., Ahn, Y.H., Yang, H. and Liu, J., 2018. Discovering proteasomal deubiquitinating enzyme inhibitors for cancer therapy: lessons from rational design, nature and old drug reposition. Future medicinal chemistry, 10(17), pp.2087-2108. doi:10.4155/fmc-2018-0091

Roma-Rodrigues, C., Mendes, R., Baptista, P.V. and Fernandes, A.R., 2019. Targeting tumor microenvironment for cancer therapy. International journal of molecular sciences, 20(4), p.840.

Srikanth, S. and Chen, Z., 2016. Plant protease inhibitors in therapeutics-focus on cancer therapy. Frontiers in pharmacology, 7, p.470.

Tan, H. Y., Wang, N., Lam, W., Guo, W., Feng, Y., and Cheng, Y. C. (2018). Targeting tumour microenvironment by tyrosine kinase inhibitor. Molecular cancer, 17(1), 43. https://doi.org/10.1186/s12943-018-0800-6

 

 

Search history

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