Rational Design Problematics of Peptide Nucleic Acids as SARS-CoV-2 Inhibitors DOI Creative Commons
Tatyana A. Grigoreva, Светлана В. Ворона, Daria Novikova

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: unknown

Published: July 16, 2024

The use of viral protein inhibitors has shown to be insufficiently effective in the case highly variable SARS-CoV-2. In this work, we examined possibility designing agents that bind a conserved region coronavirus (+)RNA. We demonstrated while design antisense RNAs is based on complementary interaction nitrogenous bases, it possible semirigid docking methods unnatural peptide nucleic acids. transition from N-(2-aminoethyl)glycine chain more conformationally rigid piperidine-containing backbone allowed us significantly increase affinity structures target RNA.

Language: Английский

Synthesis of New Organoselenium-Based Succinanilic and Maleanilic Derivatives and In Silico Studies as Possible SARS-CoV-2 Main Protease Inhibitors DOI Creative Commons
Saad Shaaban, Yasair S. Al‐Faiyz, Ghayah M. Alsulaim

et al.

Inorganics, Journal Year: 2023, Volume and Issue: 11(8), P. 321 - 321

Published: July 29, 2023

Herein we report the synthesis of organic selenide-based maleanilic and succinanilic acids in good yields (up to 95%). Their structural identities were elucidated by spectroscopic techniques (e.g., IR, 1H- & 13C-NMR, MS). The ADMET analysis, molecule electrostatic potential map, DFT, frontier molecular orbital used study organoselenium compounds’ pharmacokinetics, drug-likeness characteristics, geometries, chemical electronic properties. Moreover, a docking tool was employed investigate selenides’ ability inhibit SARS-CoV-2 Mpro target (PDB: 7BFB). Within this context, selenides exhibited promising binding affinities receptor following order (12 > 11 10 9 7 8). Furthermore, dynamics simulations also carried out for 200 ns evaluate exact behavior most active compound (12) within pocket compared with its co-crystallized inhibitor (Co).

Language: Английский

Citations

52
Ligand-Based Design on the Dog-Bone-Shaped BIBR1532 Pharmacophoric Features and Synthesis of Novel Analogues as Promising Telomerase Inhibitors with In Vitro and In Vivo Evaluations DOI
Ahmed A. Al‐Karmalawy, Mohamed S. Nafie, Moataz A. Shaldam

et al.

Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 66(1), P. 777 - 792

Published: Dec. 16, 2022

Telomerase is an outstanding biological target for cancer treatment. BIBR1532 a non-nucleoside selective telomerase inhibitor; however, it experiences ineligible pharmacokinetics. Herein, we aimed to design new BIBR1532-based analogues as promising inhibitors. Therefore, two novel series of pyridazine-linked cyclopenta[b]thiophene (8a-f) and tetrahydro-1-benzothiophene (9a-f) were synthesized. A quantitative real-time polymerase chain reaction was utilized investigate the inhibitory activity candidates. Notably, 8e 9e exhibited best inhibition profiles. Moreover, showed strong antitumor effects against both MCF-7 A549 cell lines. The on cycle apoptosis measured. Besides, evaluated its in vivo using solid Ehrlich carcinoma. reduction tumor weight volume greater than doxorubicin. Also, molecular docking ADME studies performed. Finally, SAR study conducted gain further insights into different potentials upon variable structural modifications.

Language: Английский

Citations

43
Anticoagulants as Potential SARS-CoV-2 Mpro Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies DOI Open Access
Ayman Abo Elmaaty, Wagdy M. Eldehna, Muhammad Khattab

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(20), P. 12235 - 12235

Published: Oct. 13, 2022

In this article, 34 anticoagulant drugs were screened in silico against the main protease (Mpro) of SARS-CoV-2 using molecular docking tools. Idraparinux, fondaparinux, eptifibatide, heparin, and ticagrelor demonstrated highest binding affinities towards Mpro. A dynamics study at 200 ns was also carried out for most promising anticoagulants to provide insights into dynamic thermodynamic properties compounds. Moreover, a quantum mechanical conducted which helped us attest some findings. biological evaluation (in vitro) compounds performed by carrying MTT cytotoxicity assay crystal violet order assess inhibitory concentration 50 (IC50). It is worth noting that displayed intrinsic potential inhibition with an IC50 value 5.60 µM safety index 25.33. addition, fondaparinux sodium dabigatran showed activities values 8.60 9.40 µM, respectively, indexes 17.60 15.10, respectively. Mpro enzyme investigated utilizing tipranavir as reference standard. Interestingly, attained 2.36 surpassing (IC50 = 7.38 µM) more than three-fold. Furthermore, highly eligible 10.59 µM. Finally, SAR discussed, counting on findings both vitro approaches.

Language: Английский

Citations

42
Novel 4-thiophenyl-pyrazole, pyridine, and pyrimidine derivatives as potential antitumor candidates targeting both EGFR and VEGFR-2; design, synthesis, biological evaluations, andin silicostudies DOI Creative Commons

Samia M. Al-Muntaser,

Ahmed A. Al‐Karmalawy, Abeer M. El‐Naggar

et al.

RSC Advances, Journal Year: 2023, Volume and Issue: 13(18), P. 12184 - 12203

Published: Jan. 1, 2023

In this article, we continued our previous effort to develop new selective anticancer candidates based on the basic pharmacophoric requirements of both EGFR and VEGFR-2 inhibitors. Therefore, twenty-two novel 4-thiophenyl-pyrazole, pyridine, pyrimidine derivatives were designed examined as dual EGFR/VEGFR-2 Besides, previously reported antimicrobial activities aforementioned nuclei motivated us screen their antibacterial antifungal well. First, antitumor newly synthesized evaluated against two cancer cell lines (HepG-2 MCF-7). Notably, compounds 2a, 6a, 7a, 10b, 15a, 18a exhibited superior HepG-2 MCF-7 lines. These selected further evaluate anti-EGFR anti-VEGFR-2 potentialities which found be very promising compared erlotinib sorafenib, respectively. Both 10b 2a achieved better inhibition with IC50 values 0.161 0.141 μM 0.209 0.195 μM, Moreover, most active was exact phase cycle arrest investigate mechanism death whether it due apoptosis or necrosis. On other hand, all tested Gram-positive bacteria such S. aureus B. subtilis well Gram-negative E. coli P. aeuroginosa. Also, activity investigated C. albicans A. flavus strains. The findings tests revealed that strong moderate effects. Furthermore, understand pattern by bound site, subjected different docking processes into binding sites. tried correlate compound reference drugs (erlotinib sorafenib) through DFT calculations. Finally, following biological data pyrazole, candidates, concluded a interesting SAR for optimization.

Language: Английский

Citations

29
Some pyrimidohexahydroquinoline candidates: synthesis, DFT, cytotoxic activity evaluation, molecular docking, and in silico studies DOI Creative Commons
Sayed K. Ramadan, Hisham S. M. Abd‐Rabboh,

Amal A. Abdel Hafez

et al.

RSC Advances, Journal Year: 2024, Volume and Issue: 14(23), P. 16584 - 16599

Published: Jan. 1, 2024

Hexahydroquinolines were prepared and supported by in silico studies. Thiosemicarbazide thiazolidinone derivatives showed the highest vitro antiproliferative potency against liver, breast, prostate, colon cancer cell lines.

Language: Английский

Citations

12
Investigating the possible mechanisms of pirfenidone to be targeted as a promising anti-inflammatory, anti-fibrotic, anti-oxidant, anti-apoptotic, anti-tumor, and/or anti-SARS-CoV-2 DOI
Samar A. Antar, Mohamed A. Saleh, Ahmed A. Al‐Karmalawy

et al.

Life Sciences, Journal Year: 2022, Volume and Issue: 309, P. 121048 - 121048

Published: Oct. 7, 2022

Language: Английский

Citations

34
Biological evaluation, docking studies, and in silico ADME prediction of some pyrimidine and pyridine derivatives as potential EGFR WT and EGFR T790M inhibitors DOI Creative Commons

Tarfah Al‐Warhi,

Ahmed A. Al‐Karmalawy, Ayman Abo Elmaaty

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 38(1), P. 176 - 191

Published: Nov. 1, 2022

Herein, a set of pyridine and pyrimidine derivatives were assessed for their impact on the cell cycle apoptosis. Human breast cancer (MCF7), hepatocellular carcinoma (HEPG2), larynx (HEP2), lung (H460), colon cancers (HCT116 Caco2), hypopharyngeal (FADU), normal Vero lines used. Compounds 8 14 displayed outstanding effects investigated further tested antioxidant activity in MCF7, H460, FADU, HEP2, HEPG2, HCT116, Caco2, cells by measuring superoxide dismutase (SOD), malondialdehyde content (MDA), reduced glutathione (GSH), nitric oxide (NO) content. Besides, Annexin V-FITC apoptosis detection DNA index using HEPG-2 line established both compounds as well. Furthermore, EGFR kinase (Wild T790M) inhibitory activities, revealing eligible potential. Additionally, molecular docking, ADME, SAR studies carried out candidates.

Language: Английский

Citations

28
Synthesis of SARS-CoV-2 Mpro inhibitors bearing a cinnamic ester warhead with in vitro activity against human coronaviruses DOI Creative Commons
Andrea Citarella, Davide Moi, Martina Pedrini

et al.

Organic & Biomolecular Chemistry, Journal Year: 2023, Volume and Issue: 21(18), P. 3811 - 3824

Published: Jan. 1, 2023

A panel of novel cinnamic ester derivatives showed a potent inhibitory effect against SARS-CoV-2 M pro and efficiently impaired the in vitro replication two human coronaviruses low micromolar range.

Language: Английский

Citations

19
Investigating the potential anticancer activities of antibiotics as topoisomerase II inhibitors and DNA intercalators: in vitro , molecular docking, molecular dynamics, and SAR studies DOI Creative Commons
Faten Farouk, Ayman Abo Elmaaty, Ahmed Elkamhawy

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 38(1)

Published: Jan. 26, 2023

Topoisomerase II (TOP-2) is a promising molecular target for cancer therapy. Numerous antibiotics could interact with biologically relevant macromolecules and provoke antitumor potential. Herein, docking studies were used to investigate the binding interactions of 138 against human topoisomerase II-DNA complex. Followed by MD simulations 200 ns MM-GBSA calculations. On other hand, activities most candidates investigated three cell lines using doxorubicin (DOX) as reference drug. Notably, spiramycin (SP) clarithromycin (CL) showed anticancer potentials on MCF-7 line. Moreover, azithromycin (AZ) CL exhibited good HCT-116 Finally, TOP-2 enzyme inhibition assay was carried out confirm proposed rationale. Briefly, potent inhibitory recorded erythromycin (ER) roxithromycin (RO). Additionally, SAR study opened eyes pharmacophores encountered these antibiotics.HighlightsMolecular 139 complex.SP, RO, AZ, CL, ER commercially available candidates.Molecular dynamics five complexes.MM-GBSA calculations frontier complexes.SP line, besides, AZ line.Potent RO.

Language: Английский

Citations

18
Design and statistical optimisation of emulsomal nanoparticles for improved anti-SARS-CoV-2 activity of N -(5-nitrothiazol-2-yl)-carboxamido candidates: in vitro and in silico studies DOI Creative Commons
Ahmed A. Al‐Karmalawy, Dalia S. El‐Gamil, Rabeh El‐Shesheny

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 38(1)

Published: April 24, 2023

In this article, emulsomes (EMLs) were fabricated to encapsulate the N-(5-nitrothiazol-2-yl)-carboxamido derivatives (3a-3g) in an attempt improve their biological availability and antiviral activity. Next, both cytotoxicity anti-SARS-CoV-2 activities of examined compounds loaded EMLs (F3a-g) assessed Vero E6 cells via MTT assay calculate CC50 inhibitory concentration 50 (IC50) values. The most potent 3e-loaded (F3e) elicited a selectivity index 18 with IC50 value 0.73 μg/mL. Moreover, F3e was selected for further elucidation possible mode action where results showed that it exhibited combination virucidal (>90%), viral adsorption (>80%), replication (>60%) inhibition. Besides, molecular docking MD simulations towards SARS-CoV-2 Mpro performed. Finally, structure-activity relationship (SAR) study focussed on studying influence altering size, type, flexibility α-substituent carboxamide addition compound contraction activity.HighlightsEmulsomes (3a-3g).The μg/mL against SARS-CoV-2.F3e inhibition.Molecular docking, dynamics (MD) simulations, MM-GBSA calculations performed.Structure-activity discussed

Language: Английский

Citations

14