Phytochemical Characterization of Pterocephalus frutescens with In-Silico Evaluation as Chemotherapeutic Medicine and Oral Pharmacokinetics Prediction Study DOI Creative Commons

Atef A. El‐Hela,

Marwa S. Abu Bakr, Mostafa M. Hegazy

et al.

Scientia Pharmaceutica, Journal Year: 2023, Volume and Issue: 91(1), P. 7 - 7

Published: Jan. 28, 2023

Virtual screening of the potential lead chemotherapeutic phytochemicals from medicinal plants has useful application in field in-silico modelling and computer-based drug design by orienting scoring ligands active binding site a target protein. The phytochemical investigation Pterocephalus frutescens extract n-butanol resulted isolation structure elucidation three iridoids four flavonoids which were identified as Geniposide (1), Geniposidic acid (2), Nepetanudoside C (3), Isovitexin (4), Luteolin-7-O-glucoside (5) Isoorientin (6) Orientin (7), respectively. Molecular docking studies used to compare energies isolated at biological cancer-relevant targets; namely, aromatase, carbonic anhydrase IX, fatty synthase, topoisomerase II-DNA complex. study concluded that compounds have promising cytotoxic activities, particular, (7) exhibited high affinities among sites enzymes; Aromatase (−8.73 Kcal/mol), Carbonic IX (−8.92 respectively, surpassing corresponding scores co-crystallized reference drugs these enzymes. Additionally, compounds, showed most outstanding Fatty Topisomerase complex with −6.82, −7.99 Kcal/mol, Finally, SwissADME online web tool predicted possessed acceptable oral bioavailability likeness characteristics.

Language: Английский

Design and Synthesis of 2-(4-Bromophenyl)Quinoline-4-Carbohydrazide Derivatives via Molecular Hybridization as Novel Microbial DNA-Gyrase Inhibitors DOI Creative Commons
Hany M. Abd El‐Lateef, Ayman Abo Elmaaty,

Lina M. A. Abdel Ghany

et al.

ACS Omega, Journal Year: 2023, Volume and Issue: 8(20), P. 17948 - 17965

Published: May 11, 2023

Microbial DNA gyrase is regarded as an outstanding microbial target. Hence, 15 new quinoline derivatives (5-14) were designed and synthesized. The antimicrobial activity of the afforded compounds was pursued via in vitro approaches. investigated displayed eligible MIC values, particularly against G-positive Staphylococcus aureus species. Consequently, S. supercoiling assay performed, using ciprofloxacin a reference control. Obviously, 6b 10 unveiled IC50 values 33.64 8.45 μM, respectively. Alongside, exhibited value 3.80 μM. Furthermore, significant docking binding score encountered by compound (-7.73 kcal/mol), surpassing (-7.29 kcal/mol). Additionally, both revealed high GIT absorption without passing blood brain barrier. Finally, conducted structure-activity relationship study assured usefulness hydrazine moiety molecular hybrid for either cyclic or opened form.

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
Novel fused imidazotriazines acting as promising top. II inhibitors and apoptotic inducers with greater selectivity against head and neck tumors: Design, synthesis, and biological assessments DOI
Ahmed A. Al‐Karmalawy, Mahmoud Rashed, Marwa Sharaky

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 259, P. 115661 - 115661

Published: July 18, 2023

Language: Английский

Citations

18
Design and synthesis of novel rigid dibenzo[ b,f ]azepines through ring closure technique as promising anticancer candidates against leukaemia and acting as selective topoisomerase II inhibitors and DNA intercalators DOI Creative Commons
Mohammed Farrag El‐Behairy, Walaa Hamada Abd‐Allah, Mohamed M. Khalifa

et al.

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

Published: Jan. 11, 2023

In this research, two novel series of dibenzo[b,f]azepines (14 candidates) were designed and synthesised based on the rigidification principle following reported doxorubicin's pharmacophoric features. The anti-proliferative activity was evaluated at NCI against a panel 60 cancer cell lines. Further, promising candidates (5a-g) for their ability to inhibit topoisomerase II, where 5e noticed be most active congener. Moreover, its cytotoxicity leukaemia SR cells. Also, arrested cycle G1 phase increased apoptosis ratio by 37.34%. Furthermore, in vivo studies showed inhibition tumour proliferation decrease volume. Histopathology liver enzymes examined as well. Besides, molecular docking, physicochemical, pharmacokinetic properties carried out. Finally, SAR study discussed open gate further optimisation candidate (5e).HighlightsTwo drug design.The lines.5e anti-topo II congener (IC50 = 6.36 ± 0.36 µM).5e cells cytotoxic effect confirmed 13.05 0.62 µM).In significantly inhibited 62.7% decreased volume 30.1 mm3 compared doxorubicin treatment.

Language: Английский

Citations

15
Harnessing molecular hybridization approach to discover novel quinoline EGFR-TK inhibitors for cancer treatment DOI

Noha Ryad,

Ayman Abo Elmaaty, Ibrahim M. Ibrahim

et al.

Future Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 16(11), P. 1087 - 1107

Published: May 9, 2024

Aim: Using molecular hybridization approach, novel 18 quinoline derivatives (6a–11) were designed and synthesized as EGFR-TK inhibitors. Materials & methods: The antiproliferative activity was assessed against breast (MCF-7), leukemia (HL-60) lung (A549) cancer cell lines. Moreover, the most active (6d 8b) further investigated for their potential In addition, cycle analysis apoptosis induction conducted. Results: A considerable cytotoxic attained with IC50 values spanning from 0.06 to 1.12 μM. Besides, 6d 8b displayed potent inhibitory EFGR of 0.18 0.08 μM, respectively. Conclusion: Accordingly, afforded can be used promising lead anticancer candidates future optimization.

Language: Английский

Citations

5
Thieno[2,3-b]thiophene Derivatives as Potential EGFRWT and EGFRT790M Inhibitors with Antioxidant Activities: Microwave-Assisted Synthesis and Quantitative In Vitro and In Silico Studies DOI Creative Commons

Sanaa A. Ahmed,

Moumen S. Kamel,

Moustafa O. Aboelez

et al.

ACS Omega, Journal Year: 2022, Volume and Issue: 7(49), P. 45535 - 45544

Published: Dec. 3, 2022

Microwave-assisted synthesis and spectral analysis of certain novel derivatives 3,4-diaminothieno[2,3-b]thiophene-2,5-dicarbonitrile 1-7 were carried out. Compounds examined for cytotoxicity against MCF-7 A549 cell lines using the quantitative MTT method, gefitinib erlotinib used as reference standards. shown to be more active than two tested. Compound 2 outperformed regular by 4.42- 4.12-fold in cells, respectively. The most cytotoxic compounds subsequently studied their suppression kinase activity homogeneous time-resolved fluorescence assay versus epidermal growth factor receptor (EGFRWT) EGFR790M. With IC50 values 0.28 ± 0.03 5.02 0.19, compound was demonstrated effective both forms EGFR. Furthermore, also had best antioxidant property, decreasing radical scavenging 78%. Molecular docking research, on other hand, out analyzed candidates (1-7) study mechanism action EGFR inhibitors. In silico absorption, distribution, metabolism, excretion, toxicity tests performed explain physicochemical features derivatives.

Language: Английский

Citations

18
Design and synthesis of novel quinazolinone–chalcone hybrids as potential apoptotic candidates targeting caspase-3 and PARP-1:in vitro, molecular docking, and SAR studies DOI
Eman A. Madbouly,

El‐Sayed M. Lashine,

Ahmed A. Al‐Karmalawy

et al.

New Journal of Chemistry, Journal Year: 2022, Volume and Issue: 46(46), P. 22013 - 22029

Published: Jan. 1, 2022

Novel quinazolinone–chalcone hybrids as potential apoptotic candidates targeting caspase-3 and PARP-1.

Language: Английский

Citations

18
New imidazole-2-thiones linked to acenaphythylenone as dual DNA intercalators and topoisomerase II inhibitors: structural optimization, docking, and apoptosis studies DOI Creative Commons

Asmaa H. Mohamed,

Mohammed B. Alshammari, Ashraf A. Aly

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 39(1)

Published: March 15, 2024

In this article, a new series of 2-((3,5-disubstituted-2-thioxo-imidazol-1-yl)imino)acenaphthylen-1(2H)-ones were synthesized. Imidazole-2-thione with acenaphthylen-one gave hybrid scaffold that integrated key structural elements essential for DNA damage via direct intercalation and inhibition the topoisomerase II enzyme. All synthesized compounds screened to detect their using terbium fluorescent probe. Results demonstrated 4-phenyl-imidazoles 5b 5e in addition 4-(4-chlorophenyl)imidazoles 5h 5j would induce detectable potent ctDNA. The four most as intercalators further evaluated antiproliferative activity against HepG2, MCF-7 HCT-116 utilizing MTT assay. highest anticancer was recorded breast cancer cell line which 1.5- 3- folds more active than doxorubicin, respectively. Therefore, imidazole-2-thione tethered acenaphthylenone derivatives can be considered promising development effective dual inhibitors.

Language: Английский

Citations

3
Glimepiride ameliorates renal toxicity induced by cadmium in mice: Modulation of Jun N terminal kinase (JNK)/nuclear factor kappa B (NF-κB) and phosphatidylinositol 3-kinases (PI3K)/protein kinase (AKT) pathways DOI

Mohamed Kh. ElMahdy,

Mennatallah O. Zaki,

Ahmed A. Al‐Karmalawy

et al.

Life Sciences, Journal Year: 2022, Volume and Issue: 311, P. 121184 - 121184

Published: Nov. 12, 2022

Language: Английский

Citations

14
Computational Design, Synthesis, and Bioevaluation of 2-(Pyrimidin-4-yl)oxazole-4-carboxamide Derivatives: Dual Inhibition of EGFRWT and EGFRT790M with ADMET Profiling DOI
Nilesh Raghunath Khedkar, Milind Sindkhedkar, Alex Joseph

et al.

Bioorganic Chemistry, Journal Year: 2023, Volume and Issue: 143, P. 107027 - 107027

Published: Dec. 9, 2023

Language: Английский

Citations

6