Synthesis Strategies and Medicinal Value of Pyrrole and its Fused Heterocyclic Compounds.

In the last several decades, interest in pyrrole and pyrrolopyrimidine derivatives has increased owing to their biological importance, such as anti-tumor, anti-microbial, anti-inflammatory, anti-diabetic, anti-histaminic, anti-malarial, anti-Parkinson, antioxidant and anti-viral effects, specially recently against COVID-19. These tremendous biological features have motivated scientists to discover more pyrrole and fused pyrrole derivatives, owing to the great importance of the pyrrole nucleus as a pharmacophore in many drugs, and motivated us to present this article, highlighting on the different synthetic pathways of pyrrole and its fused compounds, specially pyrrolopyrimidine, as well as their medicinal value from 2017 till 2021.

Synthesis of Some Novel Benzimidazole Derivatives as Anticancer Agent and Evaluation for CDK2 Inhibition Activity.

BACKGROUND: Thiobezimidazoles reveal various pharmacological activities due to similarities with many natural and synthetic molecules; they can easily interact with biomolecules of living systems. OBJECTIVE: A series of substituted 2-thiobezimidazoles have been synthesized. Twelve final compounds were screened for in vitro anti-cancer activities against sixty different cell lines. METHODS: The spectral data of the synthesized compounds were characterized. A docking study for active anticancer compounds and CDK2/CyclinA2 Kinase assay against standard reference; Imatinib, were performed. RESULTS: Two compounds (3c&3l) from the examined series revealed effective antitumor activity in vitro against two-cancer cell lines (Colon Cancer (HCT-116) and Renal Cancer (TK-10). The docking study of synthesized molecules discovered a requisite binding pose in the CDK-ATP binding pocket .3c &3l were promoted in the CDK2/CyclinA2 Kinase assay against standard reference Imatinib. CONCLUSION: Against all tested compounds; two compounds 3c &3l were found active against two types of cell-lines.

Synthesis of novel pyrroles and fused pyrroles as antifungal and antibacterial agents.

Pyrroles and its fused forms possess antimicrobial activities, they can easily interact with biomolecules of living systems. A series of substituted pyrroles, and its fused pyrimidines and triazines forms have been synthesised, all newly synthesised compound structures were confirmed by spectroscopic analysis. Generally, the compounds inhibited growth of some important human pathogens, the best effect was given by: 2a, 3c, 4d on Gram-positive bacteria and was higher on yeast (C. albicans), by 5c on Gram-negative bacteria and by 5a then 3c on filamentous fungi (A. fumigatus and F. oxysporum). Such results present good antibacterial and antifungal potential candidates to help overcome the global problem of antibiotic resistance and opportunistic infections outbreak. Compound 3c gave the best anti-phytopathogenic effect at a 50-fold lower concentration than Kocide 2000, introducing a safe commercial candidate for agricultural use. The effect of the compounds on DNA was monitored to detect the mode of action.

Synthesis and Evaluation of Some Uracil Nucleosides as Promising Anti-Herpes Simplex Virus 1 Agents.

Since herpes simplex virus type 1 (HSV-1) infection is so widespread, several antiviral drugs have been developed to treat it, among which are uracil nucleosides. However, there are major problems with the current medications such as severe side-effects and drug resistance. Here we present some newly synthesized cyclic and acyclic uracil nucleosides that showed very promising activity against HSV-1 compared to acyclovir.

A promising anti-cancer and anti-oxidant agents based on the pyrrole and fused pyrrole: synthesis, docking studies and biological evaluation.

A series of N-aryl derivatives of pyrrole and its related derivatives of fused form (namely; tetrahydroindole and dihydroindenopyrroles) were prepared in fair to good yields. The newly synthesized compounds were confirmed using IR, (1)H NMR, Mass spectral and elemental analysis. Tetrahydrobenzo[b] pyrroles Ia-d, 1,4-dihydroindeno[1,2-b]pyrroles IIa,b and pyrroles IIIa-c,e were evaluated for anticancer activity, coinciding with the antioxidant activity; using Di-Phenyl Picryl Hydrazyl (DPPH) tests. The cytotoxicity of the tested compounds (at a concentration of 100 and 200 µg /mL) was performed against HepG-2 and EACC cell lines. Compounds Ib, d and IIa showed promising antioxidant activity beside their anticancer activity. Docking studies were employed to justify the promising anticancer activity of Ib,d and IIa. Protein kinase (PKase)-PDB entry 1FCQ was chosen as target enzyme for this purpose using the MOLSOFT ICM 3.4-8C program. The docking results of the tested compounds went aligned with the respective anticancer assay results.