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1.
Z Naturforsch C J Biosci ; 78(3-4): 123-131, 2023 Mar 28.
Article in English | MEDLINE | ID: mdl-35993925

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Heterocyclic Compounds, 2-Ring , Tubulin/metabolism , Molecular Docking Simulation , Polymerization , Heterocyclic Compounds, 2-Ring/chemistry , Heterocyclic Compounds, 2-Ring/pharmacology , Molecular Structure , Antineoplastic Agents/pharmacology , Cell Proliferation
2.
Mini Rev Med Chem ; 22(19): 2486-2561, 2022.
Article in English | MEDLINE | ID: mdl-35339175

ABSTRACT

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.


Subject(s)
Biological Products , Chemistry, Pharmaceutical , Drug Design , Pyrroles/chemistry , Pyrroles/pharmacology , Structure-Activity Relationship
3.
Molecules ; 26(14)2021 Jul 12.
Article in English | MEDLINE | ID: mdl-34299515

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Indoles/chemical synthesis , Indoles/pharmacology , A549 Cells , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor/methods , HL-60 Cells , Humans , K562 Cells , MCF-7 Cells , PC-3 Cells , Structure-Activity Relationship
4.
Drug Res (Stuttg) ; 71(7): 388-394, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34010979

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Cytotoxins , Antineoplastic Agents/pharmacology , Apoptosis , Cell Line, Tumor , Cell Proliferation , Cytotoxins/pharmacology , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Pyrazoles/pharmacology , Structure-Activity Relationship
5.
Med Chem ; 17(5): 545-553, 2021.
Article in English | MEDLINE | ID: mdl-31808390

ABSTRACT

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.


Subject(s)
Glycoside Hydrolase Inhibitors/chemistry , Pyrroles/chemistry , alpha-Glucosidases/metabolism , Catalytic Domain , Enzyme Assays , Glycoside Hydrolase Inhibitors/chemical synthesis , Glycoside Hydrolase Inhibitors/metabolism , Kinetics , Molecular Docking Simulation , Protein Binding , Pyrroles/chemical synthesis , Pyrroles/metabolism , alpha-Glucosidases/chemistry
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