Mohammad Ashrafuddin Khan

A new series of diarylamides possessing quinoline nucleus: Synthesis, in vitro anticancer activities, and kinase inhibitory effect.

Synthesis of a new series of diarylamides possessing 6,7-dimethoxy(dihydroxy)quinoline scaffold is described. Their in vitro antiproliferative activities against NCI-58 human cancer cell lines of nine different cancer types were tested. Compounds 1a and 1d-g showed the highest mean %inhibition values over the 58 cell line panel at 10 μM, and they were further tested in 5-dose testing mode to determine their IC50 values. The five compounds were more potent than Imatinib against all the cell lines of nine different cancer types. Compound 1g showed the highest potencies. It showed inhibitory effect against C-RAF kinase (76.65% at 10 μM concentration).

Risk factors predicting complications in blood culture-proven typhoid fever in adults.

To create a prognostic model for complications of blood culture-proven typhoid fever in adults (]15 y old), a retrospective cohort was assembled though review of the medical records of the hospitalized patients treated for typhoid fever over a 3-y period ending January 1995. Of the 59 patients included, 21 (35.6%) developed various complications of typhoid fever. No patient included died. Four baseline variables (abdominal pain, systolic blood pressure B100 mmHg, hypoalbuminaemia B32 g/l and laboratory evidence of disseminated intravascular coagulation) were independently associated with complications and were used to create a prognostic model. The prediction accuracy of the model was determined using the concordance index (c-index). The results (c-index, 0.915 [95% CI, 89.0–93.0]) showed that the model predicted complications significantly better than chance. The model stratified patients into 3 prognostic stages: low risk for complications (0%; stage I), intermediate risk (42.9%; stage II) and high risk (92.3%; stage III) (p=0.001). If validated in other settings, it will help clinicians in predicting complications in patients with blood culture-proven typhoid fever on admission.To create a prognostic model for complications of blood culture-proven typhoid fever in adults (> or = 15 y old), a retrospective cohort was assembled though review of the medical records of the hospitalized patients treated for typhoid fever over a 3-y period ending January 1995. Of the 59 patients included, 21 (35.6%) developed various complications of typhoid fever. No patient included died. Four baseline variables (abdominal pain, systolic blood pressure < 100 mmHg, hypoalbuminaemia < 32 g/l and laboratory evidence of disseminated intravascular coagulation) were independently associated with complications and were used to create a prognostic model. The prediction accuracy of the model was determined using the concordance index (c-index). The results (c-index, 0.915 [95%, CI, 89.0-93.0]) showed that the model predicted complications significantly better than chance. The model stratified patients into 3 prognostic stages: low risk for complications (0%; stage I), intermediate risk (42.9%; stage II) and high risk (92.3%; stage III) (p = 0.001). If validated in other settings, it will help clinicians in predicting complications in patients with blood culture-proven typhoid fever on admission.

A Progressive Review of V600E-B-RAF-Dependent Melanoma and Drugs Inhibiting It

B-RAF gene is a component of the MAPK pathway that plays a very important role in cell division, survival, proliferation, and many other cellular functions. Mutations of the B-RAF (such as V600E-B-RAF) lead to melanoma, which is one of the leading causes of death worldwide. R&D progress is being done aiming at improved therapy in the future. The existing melanoma therapy is left out with poor overall survival, drug resistance, and many side effects. With the recent approval of new drugs, there is a hope for melanoma patients for complete cure and better life quality. However, there is still a need for improved, safe, and complete therapy for advanced melanoma. This review describes melanoma caused by V600E-B-RAF gene mutation, its pathway, drugs available and recently approved drugs, and future prospects to be overcome.