A series of novel pyrazolo[3,4-d]pyrimidines was synthesised. Twelve synthesised compounds were evaluated for their anticancer activity against 60 human tumour cell lines by NCI (USA). Compound 7d proved prominent anticancer activity. It showed 1.6-fold more potent anti-proliferative activity against OVCAR-4 cell line with IC50 = 1.74 μM. It also exhibited promising potent anticancer activity against ACHN cell line with IC50 value 5.53 μM, representing 2.2-fold more potency than Erlotinib. Regarding NCI-H460 cell line, compound 7d (IC50 = 4.44 μM) was 1.9-fold more potent than Erlotinib. It inhibited EGFR and ErbB2 kinases at sub-micromolar level (IC50 = 0.18 and 0.25 µM, respectively). Dual inhibition of EGFR and ErbB2 caused induction of apoptosis which was confirmed by a significant increase in the level of active caspase-3 (11-fold). It showed accumulation of cells in pre-G1 phase and cell cycle arrest at G2/M phase.

New ecofriendly Biginelli reaction procedures have been adapted to prepare new dihydropyrimidines (DHPMs) using a multicomponent one-pot reaction. All the synthesized compounds were evaluated for their anticancer activity against 59 human cancer cell lines and evaluated for their antimicrobial activities against representatives of both Gram-positive and Gram-negative bacteria. Compound 4 showed marked wide spectrum anticancer activity towards most of the tested cancer cell lines with a percentage of growth inhibition of 29.04-71.68% against leukemia cell line (K-562 and SR), lung cancer cell line (NCI-H522), five colon cancer cell lines (HCT-116, HCT-15, HT29, KM12 and SW-620), CNS cancer cell line (SF-295 and SNB-75), melanoma cell lines (MALME-3M and M14), renal cancer cell line (CAKI-1) and breast cancer cell lines (MCF7 and MDA-MB-468). The highest observed anticancer activity was against leukemia cell lines K-562 and SR with inhibition percentages of 64.97 and 71.68%, respectively. The renal cancer cell line (UO-31) was particularly sensitive towards all the evaluated compounds. Compounds including 2b and 5c exhibited antibacterial activity against S. aureus while 2a and 5b exhibited antifungal activity against C. albicans. The results also showed that compounds 2c and 5e exhibited both antibacterial and antifungal activity against S. aureus and C. albicans respectively.

Misramine (2), the first pentacyclic proaporphine alkaloid, has been found in Egyptian Roemeria hybrida and R. dodecandra (Papaveraceae). Sir: Over 40 naturally occurring monomeric proaporphines are known. These possess skeleton 1. In certain instances,

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Background Colorectal cancer (CRC) has a high morbidity and mortality. Many studies reported that mir‐375 is frequently down‐regulated in many cancers including esophageal cancer, hepatocellular carcinoma, breast cancer and leukemias. Aim Our aim was to study the expression of microRNA‐375 and its target gene SMAD‐7 polymorphisms (rs4939827) in CRC patients in comparison to control subjects and to correlate these results with clinical data of patients to elucidate their role in pathogenesis and early diagnosis of CRC. Material and methods The present study was conducted on 122 subjects divided into 86 patients with CRC and 36 age‐ and sex‐matched controls. The followings were done to all subjects: full history taking, full clinical examination, complete blood picture, serum (ALT, AST), serum albumin, CEA, TLC, PLT, and creatinine. Gene expression of miRNA‐375 from serum was done by real‐time PCR. Gene polymorphism SNPs of SMAD7 (rs4939827) was also done in DNA extracted from blood by real‐time PCR. Results As regards the polymorphism of SMAD7, we found that CC (wild) genotype has high percentage in controls compared to CRC cases (36.1% vs 15.1%). Meanwhile, the mutant and heterozygotes genotypes showed high percentage among cases compared to controls (33.7%, and 51.2% respectively) vs (22.2%, and 41.7% respectively) with no significant statistical analysis. There was a statistically significant high T‐allelic frequency among cases and C‐allelic frequency among controls. There was a statistically significant association between fold change in micro RNA (‐375) and the susceptibility to CRC as there is down‐regulation of the microRNA‐375 in CRC group with fold change in 0.42±0.27. Conclusion Micro RNA‐375 and rs4939827 SNP in SMAD7 could be considered as potential markers for detecting and early diagnosing CRC patients.