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The over expression of melanogenic enzymes like tyrosinase caused many hyperpigmentaion disorders. The present work describes the synthesis of hydroxy substituted 2-[(4-acetylphenyl)amino]-2-oxoethyl derivatives 3a-e and 5a-e as antimelanogenic agents. The tyrosinase inhibitory activity of synthesized derivatives 3a-e and 5a-e was determined and it was found that derivative 5c possesses excellent activity with IC 50 ¼ 0.0089 mM compared to standard kojic acid (IC 50 ¼ 16.69 mM). The presence of hydroxyl groups at the ortho and the para position of cinnamic acid phenyl ring in compound 5c plays a vital role in tyrosinase inhibitory activity. The compound 5d also exhibited good activity (IC 50 ¼ 8.26 mM) compared to standard kojic acid. The enzyme inhibitory kinetics results showed that compound 5c is a competitive inhibitor while 5d is a mixed-type inhibitor. The mode of binding for compounds 5c and 5d with tyrosinase enzyme was also assessed and it was found that both derivatives irreversibly bind with target enzyme. The molecular docking and molecular dynamic simulation studies were also performed to find the position of attachment of synthesized compounds at tyrosinase enzyme (PDB ID 2Y9X). The results showed that all of the synthesized compounds bind well with the active binding sites and most potent derivative 5c formed stable complex with target protein. The cytotoxicity results showed that compound 5c is safe at a dose of 12 mg/mL against murine melanoma (B16F10) cells. The same dose of 5c was selected to determine antimelanogenic activity; the results showed that it produced antimelenogenic effects in murine melanoma (B16F10) cells. Based on our investigations, it was proposed that compound 5c may serve as a lead structure to design more potent antimelanogenic agents.

Background: Breast cancer has the highest incidence rate among all types of cancer worldwide. There is strong evidence that delay in presentation to an oncologist may lead to a decrease in survival. Aims: This study explores factors causing diagnostic and treatment delays among the breast cancer patients enrolled in Jinnah Hospital, Lahore, from 2016 to 2018. Methods: Data from 372 patients were collected, including tumour characteristics, first symptoms, knowledge and experience of breast cancer, first visit to a doctor, etc. We calculated the patient, physician, treatment, system and total delay intervals. Results: Breast cancer cases showed longer mean patient delay in older women (> 50 years) in comparison with younger women. Women with painless lump as the initial symptom showed the longest delay with median total delay 280 days (25th and 75th percentiles 140 and 410 days respectively). Initial symptoms were correlated with total delay (P = 0.036). Educated women showed shorter delay in treatment compared with illiterate women (P = 0.068). Rural residence showed significant delay (P = 0.007). Lump size showed correlation with delay (P = 0.039). Patients with low household income (< Rs 10 000) had greater delay in diagnosis (P = 0.027) and actively employed women showed shorter delay (P < 0.0001). Unmarried women were diagnosed earlier than married (P < 0.001). Conclusions: Women showed delay in presentation due to lack of resources and lack of awareness about the disease. They presented late due to fear of surgery and chemotherapy. Using traditional treatment methods leads to diagnosis of the disease at more advanced stages.

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