scholarly journals Synthesis, Crystal Structure, Inhibitory Activity and Molecular Docking of Coumarins/Sulfonamides Containing Triazolyl Pyridine Moiety as Potent Selective Carbonic Anhydrase IX and XII Inhibitors

Crystals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1076
Author(s):  
Yassine Aimene ◽  
Romain Eychenne ◽  
Frédéric Rodriguez ◽  
Sonia Mallet-Ladeira ◽  
Nathalie Saffon-Merceron ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Carbonic Anhydrase ◽  
Inhibitory Activity ◽  
Cancer Drug ◽  
Drug Candidate ◽  
Coumarin Derivatives ◽  
X Ray Diffraction ◽  
Rhenium Complex ◽  
Pyridine Moiety ◽  
Docking Calculations

In this work, two classes of Carbonic Anhydrase (CA) inhibitors, sulfonamide and coumarin derivatives linked to pyta moiety (2a-b) and their corresponding rhenium complexes (3a-b), were designed. These compounds were synthesized and fully characterized by classical analytical methods and X-ray diffraction. All the synthesized compounds were evaluated for their inhibitory activity against the hCA isoforms I, II, IX and XII. They exhibited high inhibitory activities in the range of nanomolar for both hCA IX and hCA XII isoforms. The sulfonamide compound 2a showed the strongest inhibition against the tumour-associated hCA IX isoform with a Ki of 11.7 nM. The tumour-associated isoforms hCA IX and hCA XII were selectively inhibited by all the coumarin derivatives, with inhibition constants ranging from 12.7 nM (2b) to 44.5 nM (3b), while the hCA I and II isoforms were slightly inhibited (in the micromolar range), as expected. In terms of selectivity, compared to previously published rhenium complex-based CA inhibitors, complex 3b showed one of the highest selectivities against hCA IX and hCA XII compared to the off-target isoforms hCA I and hCA II, making it a potential anti-cancer drug candidate. Molecular docking calculations were performed to investigate the inhibition profiles of the investigated compounds at the tumour-associated hCA IX active site and to rationalize our results.

scholarly journals Crystal structure and molecular docking studies of new pyrazole-4-carboxamides

2019 ◽  
Vol 25 (1) ◽  
pp. 66-72 ◽  
Author(s):  
Li Qiao ◽  
Peng-Peng Cai ◽  
Zhong-Hua Shen ◽  
Hong-Ke Wu ◽  
Cheng-Xia Tan ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Molecular Docking ◽  
Botrytis Cinerea ◽  
Inhibitory Activity ◽  
Docking Studies ◽  
Active Group ◽  
X Ray Diffraction ◽  
X Ray ◽  
Molecular Docking Studies ◽  
H Nmr

AbstractTwo pyrazol-4-carboxamides, 3-(difluoromethyl)-N-(mesitylcarbamoyl)-1-methyl-1H-pyrazole-4-carboxa-mide (7a) and 3-(difluoromethyl)-N-((3,5-dimethylphenyl) carbamoyl)-1-methyl-1H-pyrazole-4-carboxamide (7b) were synthesized and their structures were confirmed by the aid of 1H NMR and HRMS analyses. The structure of the pyrazole-4-carboxamide, 7a was also determined by X-ray diffraction. The preliminary activity results demonstrate that these two compounds exhibit good inhibitory activity against Botrytis cinerea. Further docking results indicated that the key active group is difluoromethyl pyrazole moiety.

scholarly journals Development of Novel Quinoline-Based Sulfonamides as Selective Cancer-Associated Carbonic Anhydrase Isoform IX Inhibitors

2021 ◽  
Vol 22 (20) ◽  
pp. 11119
Author(s):  
Moataz Shaldam ◽  
Alessio Nocentini ◽  
Zainab M. Elsayed ◽  
Tamer M. Ibrahim ◽  
Rofaida Salem ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Carbonic Anhydrase ◽  
Cell Lines ◽  
Inhibitory Activity ◽  
Inhibitory Action ◽  
Docking Simulation ◽  
Simulation Studies ◽  
Molecular Docking Simulation ◽  
Anchoring Group ◽  
Mcf 7

A new series of quinoline-based benzenesulfonamides (QBS) were developed as potential carbonic anhydrase inhibitors (CAIs). The target QBS CAIs is based on the 4-anilinoquinoline scaffold where the primary sulphonamide functionality was grafted at C4 of the anilino moiety as a zinc anchoring group (QBS 13a–c); thereafter, the sulphonamide group was switched to ortho- and meta-positions to afford regioisomers 9a–d and 11a–g. Moreover, a linker elongation approach was adopted where the amino linker was replaced by a hydrazide one to afford QBS 16. All the described QBS have been synthesized and investigated for their CA inhibitory action against hCA I, II, IX and XII. In general, para-sulphonamide derivatives 13a–c displayed the best inhibitory activity against both cancer-related isoforms hCA IX (KIs = 25.8, 5.5 and 18.6 nM, respectively) and hCA XII (KIs = 9.8, 13.2 and 8.7 nM, respectively), beside the excellent hCA IX inhibitory activity exerted by meta-sulphonamide derivative 11c (KI = 8.4 nM). The most promising QBS were further evaluated for their anticancer and pro-apoptotic activities on two cancer cell lines (MDA-MB-231 and MCF-7). In addition, molecular docking simulation studies were applied to justify the acquired CA inhibitory action of the target QBS.

scholarly journals Molecular Docking and Virtual Screening based prediction of drugs for COVID-19

2020 ◽  
Vol 23 ◽  
Author(s):  
Sekhar Talluri
Keyword(s):  
Clinical Trials ◽  
Molecular Docking ◽  
Virtual Screening ◽  
Genomic Sequence ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
X Ray Diffraction ◽  
Main Protease ◽  
Docking Calculations ◽  
Approved Drugs

Aims: To predict potential drugs for COVID-19 by using molecular docking for virtual screening of drugs approved for other clinical applications. <p> Background: SARS-CoV-2 is the betacoronavirus responsible for the COVID-19 pandemic. It was listed as a potential global health threat by WHO due to high mortality, high basic reproduction number and lack of clinically approved drugs and vaccines for COVID-19. The genomic sequence of the virus responsible for COVID-19, as well as the experimentally determined three dimensional structure of the Main protease are available. <p> </p> Objective: To identify potential drugs that can be repurposed for treatment of COVID-19 by using molecular docking based virtual screening of all approved drugs. <p> </p> Methods: List of drugs approved for clinical use was obtained from SuperDRUG2 database. The structure of the target in the apo form, as well as structures of several target-ligand complexes, were obtained from RCSB PDB. The structure of SARS-CoV-2 Mpro determined from X-ray diffraction data was used as the target. Data regarding drugs in clinical trials for COVID-19 was obtained from clinicaltrials.org. Input for molecular docking based virtual screening was prepared by using Obabel and customized python, bash and awk scripts. Molecular docking calculations were carried out with Vina and SMINA, and the docked conformations were analyzed and visualized with PLIP, Pymol and Rasmol. <p> </p> Results: Among the drugs that are being tested in clinical trials for COVID-19, Danoprevir and Darunavir have the highest binding affinity for the target main protease of SARS-CoV-2. Saquinavir and Beclabuvir were identified as the best novel candidates for COVID-19 therapy by using Virtual Screening of drugs approved for other clinical indications. <p> </p> Conclusion: Protease inhibitors approved for treatment of other viral diseases have the potential to be repurposed for treatment of COVID-19. </p>

Synthesis, Molecular Docking and Pharmacological Investigation of Heterocyclic Amine Derivatives as Potential Anticancer Agents

2021 ◽  
Author(s):  
Ahmed Sadiq Sheikh ◽  
Humaira Nadeem ◽  
Mahboob Alam ◽  
Muhammad Tariq Khan ◽  
Ameer Khusro ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Carbonic Anhydrase ◽  
Anticancer Agents ◽  
Inhibitory Activity ◽  
Chemotherapeutic Agents ◽  
New Drugs ◽  
Heterocyclic Amine ◽  
Life Threatening ◽  
Inhibitory Potential

Abstract Cancer is life threatening disease that causes great damage to health worldwide. Studies shown that hypoxia is the major contributor to tumor and cancer development due to overexpression of carbonic anhydrase. To encounter such cells abnormalities, demanding new drugs or novel analogs of currently in use. Therefore, the search for new pharmacoactive moieties with considerable effective activity against such tumors and cancers is needed. The implication of heterocyclic amine and acetamide derivatives well known as chemotherapeutic agents. Heterocyclic amine morpholine was taken as principal products and its new derivatives were synthesized after being designed computationally via molecular docking. A series of some of its new synthetic analogs i.e heterocyclic amine derivatives 1(a-o) were successfully synthesized and screened for their anticancer and carbonic anhydrase inhibitory potential. Most of the compounds showed good results possessing reasonable carbonic anhydrase inhibitory activity particularly compounds 1c, 1d, 1h and 1i showed very reasonable carbonic anhydrase inhibitory activity whereas compound 1h showed maximum inhibition comparable to acetazolamide. Similarly, four of the synthesized compounds showed good anticancer activity particularly compound 1b, 1c, 1h, and 1i showed reasonable, whereas compound 1h have better IC50 value comparable to cisplatin when evaluated via in vitro MTT assay.

scholarly journals Assessment of dual inhibitory activity of epifriedelanol isolated from Cayratia trifolia against ovarian cancer

2016 ◽  
Vol 11 (2) ◽  
pp. 545 ◽  
Author(s):  
Palanisamy Chella Perumal ◽  
Sundaram Sowmya ◽  
Devadasan Velmurugan ◽  
Thirunavukkarasu Sivaraman ◽  
Velliyur Kanniappan Gopalakrishnan
Keyword(s):  
Ovarian Cancer ◽  
Molecular Docking ◽  
Inhibitory Activity ◽  
Ethanolic Extract ◽  
Bioactive Compound ◽  
Cancer Drug ◽  
Binding Affinities ◽  
Protein Targets ◽  
X Ray ◽  
Cayratia Trifolia

<p class="Abstract"><em>Cayratia trifolia</em> is used as diuretic, in tumors, neuralgia and splenopathy. However, compounds depicting anti-ovarian cancer activities from this plant source have not yet been identified and structurally characterized till date. In the present study, X-ray structure of epifriedelanol, a bioactive compound, isolated from the ethanolic extract of the <em>C. trifolia</em> and its binding affinities against a few proteins (HER2, EGFR and CXCR4) that are reported to get overexpressed under ovarian cancer had been thoroughly studied by using molecular docking means. Binding affinities of the compound vis-à-vis that of carboplatin, a FDA approved drug to the ovarian cancer, to interact with the protein targets are quite impressive. The drug-likeness properties of the epifriedelanol and scope to develop the compound as a potent anti-ovarian cancer drug are discussed in this paper.</p><p> </p>

scholarly journals Size and Flexibility Define the Inhibition of the H3N2 Influenza Endonuclease Enzyme by Calix[n]arenes

Antibiotics ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 73 ◽  
Author(s):  
Yannick Tauran ◽  
José Pedro Cerón-Carrasco ◽  
Moez Rhimi ◽  
Florent Perret ◽  
Beomjoon Kim ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Site ◽  
Inhibitory Activity ◽  
Water Soluble ◽  
Endonuclease Activity ◽  
Ic50 Value ◽  
Docking Calculations ◽  
H3n2 Influenza ◽  
Theoretical Results ◽  
Endonuclease Enzyme

Inhibition of H3N2 influenza PA endonuclease activity by a panel of anionic calix[n]arenes and β-cyclodextrin sulfate has been studied. The joint experimental and theoretical results reveal that the larger, more flexible and highly water-soluble sulfonato-calix[n]arenes have high inhibitory activity, with para-sulfonato-calix[8]arene, SC8, having an IC50 value of 6.4 μM. Molecular docking calculations show the SC8 can interact at both the polyanion binding site and also the catalytic site of H3N2 influenza PA endonuclease.

Design, Synthesis, Molecular Docking and Biological Evaluation of 1-(benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol Derivatives as Antiproliferative Agents

2019 ◽  
Vol 16 (10) ◽  
pp. 837-845
Author(s):  
Sandhya Jonnala ◽  
Bhaskar Nameta ◽  
Murthy Chavali ◽  
Rajashaker Bantu ◽  
Pallavi Choudante ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inhibitory Activity ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Mouse Skin ◽  
Coupling Reaction ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Design Synthesis

A class of 1-((benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol derivatives (4a-t) has been synthesized in good yields through a three component coupling reaction. The newly synthesized compounds were evaluated for their in vitro antiproliferative activity against five cell lines such as DU145 (human prostate cancer), MDA-MB-B231 (human breast cancer), SKOV3 (human ovarian cancer), B16-F10 (mouse skin melanoma) and CHO-K1 (Chinese hamster ovary cells), a noncancerous cell line. In vitro inhibitory activity indicates that compounds 4a, 4b, 4c, 4d, 4g, 4j, and 4o exhibited potent anti-proliferative behavior. Among them, compounds 4g, 4j and 4o found to be the most active members exhibiting remarkable growth inhibitory activity. Molecular docking facilitates to investigate the probable binding mode and key active site interactions in tubulins α and β proteins. The docking results are complementary to experimental results.

Sign in / Sign up

Export Citation Format

Share Document