Synthesis and Cytotoxic Activity Study of Novel 2-(Aryldiazenyl)-3-methyl-1H-benzo[g]indole Derivatives.

A novel series of 2-(aryldiazenyl)-3-methyl-1H-benzo[g]indole derivatives (3a-f) were prepared through the cyclization of the corresponding arylamidrazones, employing polyphosphoric acid (PPA) as a cyclizing agent. All of the compounds (3a-f) were characterized using 1H NMR, 13C NMR, MS, elemental analysis, and melting point techniques. The synthesized compounds were evaluated for cytotoxic activity against diverse human cancer cell lines by the National Cancer Institute. While all of the screened compounds were found to be cytotoxic at a 10 µM concentration, two of them (2c) and (3c) were subjected to five dose screens and showed a significant cytotoxicity and selectivity.

Potent α-glucosidase inhibitors with benzimidazole-propionitrile hybridization; synthesis, bioassay and docking study.

Background: Diabetes is characterized by a lack of insulin and insensitivity to insulin. In 2013, the global diabetes population was 382 million, with 90% of them having type 2 diabetes (non-insulin-dependent). It is predicted that this number will increase to 592 million by 2035.Aim: Here, we aimed to synthesize a series of benzimidazole-based derivatives B1-B32 with α-glucosidase inhibition potential as antidiabetic agents.Methods: Compounds B1-B32 were prepared in three three-step reactions, and the structures were elucidated using spectroscopic methods, namely 1H NMR, 13C NMR, MS and IR. Enzyme inhibition and kinetic study were done using commercial assay kits, and molecular docking study using autodock4.Results: Bioassay data showed that twenty-four out of the thirty-two tested compounds exhibited IC50 values ranging from 44 to 745 µM, surpassing the standard molecule, acarbose (IC50: 750 µM). it was determined that the best compound, B10, functions as a competitive inhibitor. Additionally, a molecular docking study provided insights into the interactions between the four most promising compounds (B5, B6, B10 and B28) and the active site residues within the enzyme.Conclusion: The tested compounds are interesting α-glucosidase inhibitors, which indicates the benefit of more bioassay studies, especially in vivo studies.

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Benzimidazole-acrylonitrile hybrid derivatives act as potent urease inhibitors with possible fungicidal activity.

Aim: A series of benzimidazole-acrylonitrile derivatives TM1-TM53 were designed with urease inhibition approach.Materials & methods: TM1-TM53 were synthesized and characterized (1H Nuclear Magnetic Resonance (NMR), 13C NMR, Mass Spectroscopy (MS) and IR) and subjected to urease inhibition assay using commercial assay kit. A molecular docking study was also performed using Autodock tool software.Results: Except six compounds, target molecules exhibited a higher urease inhibition effect (IC50: 1.22-28.45 µM) than hydroxyurea (IC50: 100 µM). kinetic study on TM11, clarified its mode of action as a mixed inhibitor. A molecular docking study on TM6, TM11 and TM21, was performed and the results showed the main residues inside the active site of the enzyme. All TM1-TM53 were also studied in silico using molecular docking techniques to evaluate their potential to inhibit succinate dehydrogenase in comparison to fluxapyroxad as standard. Docking study revealed the high potential of TM1-TM53 as a fungicides.Conclusion: Obtained results exhibited the high activity of benzimidazole-acrylonitrile derivatives as urease inhibitors and their possible potential as fungicide agents. So, it will be beneficial to do more bioactivity investigation on this family of compounds.

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Design, synthesis, and molecular docking study of novel cinnoline derivatives as potential inhibitors of tubulin polymerization.

The preparation of a novel 4-methylbenzo[h] cinnolines entity via a three-step synthetic protocol is described. Cyclization of the naphthylamidrazones, in the presence of polyphosphoric acid (PPA), furnishes the respective target benzo[h]cinnolines directly. This one-pot synthesis involves intramolecular Friedel-Crafts acylation followed by instant elimination under heating conditions. It is noteworthy that the yield of the product from this step decreases dramatically if the heating is extended beyond 3 h. The target novel cinnolone derivatives were identified by mass spectrometry and their structures elucidated by spectroscopic techniques. Subsequently, molecular docking was performed to shed light on the putative binding mode of the newly synthesized cinnolines. The docking results indicate that these derivatives are potential inhibitors of tubulin polymerization and the best interaction was achieved with a computational ki = 0.5 nM and posed correctly over the lexibulin.

An Approach to Pharmacological Targets of Pyrrole Family From Medicinal Chemistry Viewpoint.

Pyrrole is one of the most widely used heterocycles in the pharmaceutical industry. Due to the importance of pyrrole structure in drug design and development, herein, we tried to conduct an extensive review of the bioactive pyrrole-based compounds reported recently. The bioactivity of pyrrole derivatives varies, so in the review, we categorized them based on their direct pharmacologic targets. Therefore, readers are able to find the variety of biological targets for pyrrole-containing compounds easily. This review explains around seventy different biologic targets for pyrrole-based derivatives, so it is helpful for medicinal chemists in the design and development of novel bioactive compounds for different diseases. This review presents an extensive, meaningful structure-activity relationship for each reported structure as much as possible. The review focuses on papers published between 2018 and 2020.

Triarylpyrazole Derivatives as Potent Cytotoxic Agents; Synthesis and Bioactivity Evaluation "Pyrazole Derivatives as Anticancer Agent".

BACKGROUND: During the last recent years, several anti-cancer agents were introduced for the treatment of diverse kinds of cancer. Despite their potential in the treatment of cancer, drug resistance and adverse toxicity such as peripheral neuropathy are some of the negative criteria of anti-cancer agents and for this reason, the design and synthesis of new anti-cancer agents are important. OBJECTIVE: Design, synthesis, and anticancer activity evaluation of some pyrazole derivatives. METHODS: A series of Target compounds were prepared using multistep synthesis. Their cytotoxic activity against three different human cancer cell lines namely human colon carcinoma cells (HT-29), epithelial carcinoma cells (U-87MG), pancreatic cancerous cells (Panc-1) as well as AGO1522 normal cell line using in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was investigated. RESULTS: 1,3-Diaryl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole and 1,3-Diaryl-5-(3,4,5-trimethoxyphenyl)- 1H-pyrazole were synthesized in good yields and their structure and purity were confirmed using 1H-NMR, 13C-NMR, and elemental analysis. Generally, the synthesized scaffolds exhibited good cytotoxicity against cancerous cell lines in comparison to the reference standard, paclitaxel. Compounds 3A: and 3C: , in Annexin V/ PI staining assay, exerted remarkable activity in apoptosis induction in HT-29 cell lines. Both of them also led to cell cycle arrest in the sub-G1 phase which is inconsistent with the results of apoptosis assay. CONCLUSION: Concerning obtained results, it is interesting to synthesis more pyrazole derivatives as anticancer agents.

Study on the Interaction of 1,5-diaryl Pyrrole Derivatives with α- glucosidase; Synthesis, Molecular Docking, and Kinetic Study.

BACKGROUND: The delaying of absorption of glucose is one of the principal therapeutic approaches of type 2 diabetes. α-glucosidase inhibitors compete with the α-glucosidase enzyme activity, which helps to reduce the conversion of carbohydrates into glucose and thereby control the postprandial hyperglycemia incidence. OBJECTIVE: The aim of this study was to synthesize a series of novel 1,5-diphenyl pyrrole derivatives and evaluate their in vitro α-glucosidase inhibitory activities. METHODS: Compounds were synthesized through a multistep reaction and were evaluated for α- glucosidase inhibitory activities. Molecular docking and kinetic studies were carried out to predict the mode of binding and mechanism of inhibition for the most active compounds, 5g and 5b, against α-glucosidase. RESULTS: Synthesized compounds showed good in vitro α-glucosidase inhibitory activity with IC50 values in the range of (117.5 ± 3.8 to 426.0 ± 10.2 µM) as compared to acarbose, the standard drug, (750 ± 8.7 µM). Compound 5g (117.5 ± 3.8 µM) ascertained as the most potent inhibitor of α-glucosidase in a competitive mode. The binding energies of compounds 5g and 5b (119.0 ± 7.5 µM), as observed from the best docking conformations, indicate that they have a lower free binding energy (-3.26 kcal/mol and -3.0 kcal/mol, respectively) than acarbose (2.47 kcal/mol). CONCLUSION: The results of our study revealed that the synthesized compounds are a potential candidate for α-glucosidase inhibitors for the management of postprandial hyperglycemia for further investigation.