DFT calculations and POM analyses of cytotoxicity of some flavonoids from aerial parts of Cupressus sempervirens: Docking and identification of pharmacophore sites

Elsharkawy, Eman; Almalki, Faisal A.; Hadda, Taïbi Ben; Rastija, Vesna; Lafridi, Hind; Zgou, H.

doi:10.1016/j.bioorg.2020.103850

Cited by 19 publications

(6 citation statements)

References 28 publications

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“…The reactivity of the molecule can be demonstrated by the distribution of the orbital frontiers which is predicted with the help of the frontier molecular orbital (FMO) theory. The frontier orbital gap helps to characterize the chemical reactivity and kinetic stability 43 of the molecules. The HOMO and the LUMO determine the way by which it interacts with other species.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Theoretical Studies on the Molecular Properties, Toxicity, and Biological Efficacy of 21 New Chemical Entities

Srivastava

2021

ACS Omega

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New chemical entities (NCEs) such as small molecules and antibody–drug conjugates have strong binding affinity for biological targets, which provide deep insights into structure-specific interactions for the design of future drugs. As structures of drugs increase in complexity, the importance of computational predictions comes into sharp focus. Knowledge of various computational tools enables us to predict the molecular properties, toxicity, and biological efficacy of the drugs and help the medicinal chemists to discover new drugs more efficiently. Newly approved drugs have higher affinities for proteins and nucleic acids and are applied for the treatment of human diseases. We have carried out the computational studies of 21 such NCEs, specifically small molecules and antibody–drug conjugates, and studied the biological efficacy of these drugs. Their bioactivity score and molecular and pharmacokinetic properties were evaluated using online computer software programs, viz., Molinspiration and Osiris Property Explorer. The SwissTargetPrediction tool was used for the efficient prediction of protein targets for the NCEs. The results indicated higher stability for the drug complexes due to a larger HOMO–LUMO gap. A high electrophilicity index reflects good electrophilic behavior and high reactivity of the drugs. Lipinski’s ‘‘rule of five’’ indicated that most of the drug complexes are likely to be orally active. These drugs also showed non-mutagenic, non-tumorigenic, non-irritant, and non-effective reproductive behavior. We hope that these studies will provide an insight into molecular recognition and definitely help the medicinal chemists to design new drugs in future.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Theoretical Studies on the Molecular Properties, Toxicity, and Biological Efficacy of 21 New Chemical Entities

Srivastava

2021

ACS Omega

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“…The results of our previous docking study of quinoline-arylamidine hybrids with c-Src revealed that the key interactions are the H-bonds between the amino groups from the 2-aminoethanol linker, Asp404 and the quinoline nitrogen atom, and Tyr382 and with Tyr340 via nitrogen from the nitrile group [ 29 ]. Apigenin glycoside isolated from Cupressus sempervirens creates a hydrogen bond via the hydroxyl group of a glucopyranose ring with Val402 and Val323, while the second hydroxyl group creates hydrogen bonds with Tyr382 and Asp404 [ 65 ]. A docking study of azaacridine derivatives revealed that the amido moiety also formed two hydrogen bonds with Glu310 and Asp404 and three π-π interaction bonds and one cation–π bond with Leu 273, Phe 405, Tyr 382, and Lys 295, respectively [ 66 ].…”

Section: Resultsmentioning

confidence: 99%

Novel 7-Chloro-4-aminoquinoline-benzimidazole Hybrids as Inhibitors of Cancer Cells Growth: Synthesis, Antiproliferative Activity, in Silico ADME Predictions, and Docking

et al. 2023

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In this study, new 7-chloro-4-aminoquinoline-benzimidazole compounds were synthesized and characterized by NMR, MS, and elemental analysis. These novel hybrids differ in the type of linker and in the substituent on the benzimidazole moiety. Their antiproliferative activities were evaluated on one non-tumor (MDCK1) and seven selected tumor (CaCo-2, MCF-7, CCRF-CEM, Hut78, THP-1, and Raji) cell lines by MTT test and flow cytometry analysis. The compounds with different types of linkers and an unsubstituted benzimidazole ring, 5d, 8d, and 12d, showed strong cytotoxic activity (the GI50 ranged from 0.4 to 8 µM) and effectively suppressed the cell cycle progression in the leukemia and lymphoma cells. After 24 h of treatment, compounds 5d and 12d induced the disruption of the mitochondrial membrane potential as well as apoptosis in HuT78 cells. The drug-like properties and bioavailability of the compounds were calculated using the Swiss ADME web tool, and a molecular docking study was performed on tyrosine-protein kinase c-Src (PDB: 3G6H). Compound 12d showed good solubility and permeability and bound to c-Src with an energy of −119.99 kcal/mol, forming hydrogen bonds with Glu310 and Asp404 in the active site and other residues with van der Waals interactions. The results suggest that compound 12d could be a leading compound in the further design of effective antitumor drugs.

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“…Now, it becomes easier, by using the POM (Petra/Osiris/Molinspiration) Theory, to identify and to optimize most of the antibacterial [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , antifungal [50] , [51] , [52] , antiviral [53] , [54] , [55] , antiparasital [ 56 , 57 ], and antitumor [58] , [59] , [60] pharmacophore sites, one by one, on the basis of their different physico-chemical parameters and their different electronic charge repartition of corresponding heteroatoms. This young POM Theory was extended to other various and different biotargets [ 61 , 62 ].…”

Section: Resultsmentioning

confidence: 99%

Crystallographic study, biological assessment and POM/Docking studies of pyrazoles-sulfonamide hybrids (PSH): Identification of a combined Antibacterial/Antiviral pharmacophore sites leading to in-silico screening the anti-Covid-19 activity

Chalkha

Nakkabi

Hadda

et al. 2022

Journal of Molecular Structure

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DFT calculations and POM analyses of cytotoxicity of some flavonoids from aerial parts of Cupressus sempervirens: Docking and identification of pharmacophore sites

Cited by 19 publications

References 28 publications

Theoretical Studies on the Molecular Properties, Toxicity, and Biological Efficacy of 21 New Chemical Entities

Theoretical Studies on the Molecular Properties, Toxicity, and Biological Efficacy of 21 New Chemical Entities

Novel 7-Chloro-4-aminoquinoline-benzimidazole Hybrids as Inhibitors of Cancer Cells Growth: Synthesis, Antiproliferative Activity, in Silico ADME Predictions, and Docking

Crystallographic study, biological assessment and POM/Docking studies of pyrazoles-sulfonamide hybrids (PSH): Identification of a combined Antibacterial/Antiviral pharmacophore sites leading to in-silico screening the anti-Covid-19 activity

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