Phthalimide derivatives are a versatile scaffold for designing novel drug candidates and have shown promise in treating a variety of diseases, including cancer. Cancer remains a devastating disease, demanding continued research and improved treatment strategies due to its severe adverse effects. This study employs computational and experimental techniques to investigate the properties and potential biological activity of N-hydroxymethyl phthalimide. DFT calculations, using B3LYP (functional) with a basis set, 6311++G(d,p), were utilized in Structural analysis, Topological studies, and Biological evaluation. Molecular geometry and FT-IR and FT-Raman spectroscopy were employed to characterize the structural properties of compound. Topological analysis (MEP, ELF, LOL) was performed. To assess potential biological activity of N-hydroxymethyl phthalimide, UV-Vis analysis, FMO analysis, drug-likeness, and molecular docking studies were conducted. In vitro, cytotoxicity assays were also performed to evaluate the compound's cytotoxic effect on human skin melanoma cell-line. Results predict that N-hydroxymethyl phthalimide exhibits anti-cancer activity, indicating its potential as a promising agent for inhibiting cancer.

Keywords: Phthalimides; Drug-Likeness Properties; In Vitro Assay Studies; Molecular Docking; Anti-Cancer Activity; Skin Melanoma

References

1. World Health Organisation. Global Health observatory. Available: Geneva: World Health Organisation (2018).
2. Agrawal N., et al. “Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1”. Science 333 (2011): 1154-1157.
3. Abrahao R., et al. “Predictors of survival after head and neck squamous cell carcinoma in South America: the Inter Change study”. JCO Global Oncology 6 (2020): 486-99.
4. Seigel RL., et al. “Cancer Statistics”. CA: A Cancer Journal for Clinicians 1 (2021): 7-33.
5. Bahl A., et al. “Prevalence and trends of human papillomavirus in oropharyngeal cancer in a predominantly North Indian population”. Head Neck 36 (2014): 505-510.
6. Deschler DG., et al. “The "new" head and neck cancer patient-young, nonsmoker, nondrinker, and HPV positive: Evaluation”. Otolaryngology-Head and Neck Surgery 151 (2014): 375-380.
7. Dillon MT, Harrington KJ. “Human papillomavirus-negative pharyngeal cancer”. Journal of Clinical Oncology 33 (2015): 3251-3261.
8. Kreimer A., et al. “Humar Paillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review”. Cancer Epidemiology, Biomarkers and Prevention 14 (2004): 467-475.
9. Mohan M and Jagannathan N. “Oral field cancerization: an update on current concepts”. Oncology Reviews1 (2014).
10. Bray F., et al. “Global Cancer statistics 2018: GLOBANCON estimates of incidence and mortality worldwide for 36 cancers in 185 countries”. CA: A Cancer Journal for Clinicians 6) (2018): 394-424.
11. Shield KD., et al. “The global incidence of lip, oral cavity, and pharyngeal cancers by subsite in 2012”. CA: A Cancer Journal for Clinicians 67 (2017): 51-64.
12. Mehanna H., et al. “Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer-systematic review and meta-analysis of trends by time and region”. Head Neck 35 (2013): 747-755.
13. Gillison ML., et al. “Epidemiology of Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma”. Journal of Clinical Oncology 33 (2015): 3235-3242.
14. Global Burden of Disease Cancer Collaboration. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study”. JAMA Oncology 3 (2017): 524-548.
15. Miranda-Filho A and Bray F. “Global patterns and trends in cancers of the lip, tongue and mouth”. Oral Oncology 102 (2020): 104551.
16. Vigneswaran N and Williams MD. “Epidemiologic trends in head and neck cancer and aids in diagnosis”. Oral and Maxillofacial Surgery Clinics of North America 2 (2014): 123-141.
17. Chi AC., et al. “Oral cavity and oropharyngeal squamous cell carcinoma--an update”. CA: A Cancer Journal for Clinicians 65 (2015): 401-421.
18. Virnig BA., et al. “Studying radiation therapy using SEER-Medicare-linked data”. Medical Care 40 (2002): 49.
19. Barton MB., et al. “Estimating the demand for radiotherapy from the evidence: a review of changes from 2003 to 2012”. Radiotherapy and Oncology 112 (2014): 140-144.
20. Van der Molen L., et al. “Functional outcomes and rehabilitation strategies in patients treated with chemoradiotherapy for advanced head and neck cancer: a systematic review”. European Archives of Oto-Rhino-Laryngology 266 (2009): 889-900.
21. Hashibe M., et al. “Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium”. Cancer Epidemiology, Biomarkers and Prevention 18 (2009): 541-550.
22. net Fact Sheet: Head and neck cancer: statistics (2022).
23. Hobbs CGL., et al. “Human papillomavirus and head and neck cancer: a systematic review and meta-analysis”. Clinical Otolaryngology 31 (2006): 259-266.
24. Miyaishi O., et al. “Cancer incidence in old age”. Mechanisms of Ageing and Development1-3 (2000): 47-55.
25. Johnson NW., et al. “Squamous cell carcinoma and precursor lesions of the oral cavity: Epidemiology and aetiology”. Periodontology 2000 57 (2011): 19‑37.
26. Das Gupta S., et al. “Clinicopathological profile of head and neck squamous cell carcinoma”. Indian Journal of Medical and Paediatric Oncology 03 (2019): 369-373.
27. , et al. “Demographic profile and risk factors of head-and-neck squamous cell carcinoma in west Tamil Nadu: A cross-sectional observational study”. Cancer Research Statistics and Treatment 6.2 (2023): 215-223.
28. Preetham A Puthukudy and M Feshan. “Clinicopathological profile and outcomes of treatment of head and neck cancer patients in a tertiary care center: a hospital-basd prospective study”. International Journal of Otorhinolaryngology and Head and Neck Surgery 1 (2002): 58-64.
29. Chauhan JP., et al. “Laryngeal cancer: a clinicopathological study of 65 cases”. International Journal of Otorhinolaryngology and Head and Neck Surgery 1 (2018): 163-168.
30. Siddiqui MS., et al. “Epidemiology and histopathological spectrum of head and neck cancers in Bihar, a state of Eastern India”. Asian Pacific Journal of Cancer Prevention8 (2012): 3949-3953.v
31. Shanghvi LD., et al. “Epidemiology of head and neck cancers”. Seminars in Surgical Oncology5 (1989): 305-309.
32. Kalyani R., et al. “Pattern of cancer in adolescent and young adults‑‑A ten year study in India”. Asian Pacific Journal of Cancer Prevention 11 (2010): 655‑659.
33. Alam MS., et al. “Epidemiological profile of head and neck cancer patients in Western Uttar Pradesh and analysis of distributions of risk factors in relation to site of tumor”. Journal of Cancer Research and Therapeutics 13 (2017): 430‑435.
34. Bobdey S., et al. “Squamous cell carcinoma of buccal mucosa: An analysis of prognostic factors”. South Asian Journal of Cancer 7 (2018): 49-54.
35. Krishna A., et al. “Demographic risk factors, affected anatomical sites and clinicopathological profile for oral squamous cell carcinoma in a north Indian population”. Asian Pacific Journal of Cancer Prevention 15 (2014): 6755-6760.
36. Goud ML., et al. “Epidemiological correlates between consumption of Indian chewing tobacco and oral cancer”. European Journal of Epidemiology 02 (1990): 219-222.
37. Pednekar MS., et al. “Association of tobacco habits, including bidi smoking, with overall and site-specific cancer incidence: results from the Mumbai cohort study”. Cancer Causes Control 06 (2011): 859-868.
38. Chauhan R., et al. “A Study of Head and Neck Cancer Patients with Reference to Tobacco Use, Gender, and Subsite Distribution”. South Asian Journal of Cancer 1 (2002): 46-51.
39. Sharma JD., et al. “Burden of head and neck cancers in Kamrup urban district cancer registry of Assam, India: A retrospective study”. International Journal of Research in Medical Sciences 2 (2014): 1382‑1387.
40. Sapkota A., et al. “Smokeless tobacco and increased risk of hypopharyngeal and laryngeal cancers: Amulticentric case control study from India”. International Journal of Cancer 121 (2007): 1793-1798.
41. Dhull Ak., et al. “Major risk factors in head and neck cancer: A retrospective analysis of 12-year experiences”. World Journal of Clinical Oncology 9 (2018): 80-84.
42. Addala L., et al. “Risk factor profiles of head and neck cancer patients of Andhra Pradesh, India”. Indian Journal of Cancer 49 (2012): 215-219.
43. Maasland DH., et al. “Alcohol consumption, cigarette smoking and the risk of subtypes of head neck cancer: Results from the Netherlands Cohort Study”. BMC Cancer 14 (2014): 187.
44. Auguste A., et al. “Head and neck cancer risk factors in the French West Indies”. BMC Cancer 21 (2021): 1071.
45. Consumption of Tobacco in India, 1993‑94: 5^th Quinquennial survey of consumer expenditure: NSS 50^th round, July 1993‑ June 1994. 1998; National Sample Survey organization, `Dept. of Statistics, Govt. of India (1993).
46. Raja BK and Devi VNK. “Prevalence of tobacco use among school‑going adolescents in India: A systematic review of the literature”. Cancer Research, Statistics, and Treatment 1 (2018): 110‑115.
47. Ghiet T., et al. “Role of mucosal high-risk human papillomavirus types in head and neck cancers in central india”. International Journal of Cancer 141 (2017): 143-151.
48. Bandhary SK., et al. “Detection of human papilloma virus and risk factors among patients with head and neck squamous cell carcinoma attending a tertiary referral centre in South India”. Asian Pacific Journal of Cancer Prevention 19 (2018): 1325-1330.
49. Laprise C., et al. “No role for human papillomavirus infection in oral cancers in a region in southern India”. International Journal of Cancer 138 (2016): 912-917.
50. Mohanti BK., et al. “Analysis of 2167 head and neck cancer patients’ management, treatment compliance and outcomes from regional cancer centre, Delhi, India”. The Journal of Laryngology and Otology 121 (2007): 49-56.
51. Sharma A., et al. “Compliance to therapy-elderly head and neck carcinoma patients”. Canadian Geriatrics Journal 17 (2014): 83-87.
52. Pandey KC., et al. “Evaluation of factors in relation with the non-compliance to curative intent radiotherapy among patients of head and neck carcinoma. A study from the Kumraon region of India”. Indian Journal of Palliative Care 21 (2015): 21-26.
53. Kao J., et al. “Association of radiation does intensity with overall survival in patients with distant metastases”. Cancer Medicine22 (2021): 7394-7342.

Citation

Citation: Johanan Christian Prasana., et al. “Structural Analysis, Topological Studies and Biological Evaluation on N-hydroxymethyl Phthalimide - an Insight into Anticancer Activity”.Acta Scientific Cancer Biology 9.1 (2025): 37-52.

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Copyright: © 2025 Johanan Christian Prasana., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.