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Synthesis, In Silico Prediction, and In Vitro Evaluation of Anti-tumor Activities of Novel 4'-Hydroxybiphenyl-4-carboxylic Acid Derivatives as EGFR Allosteric Site Inhibitors
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Introduction:

Allosteric inhibition of EGFR tyrosine kinase (TK) is currently among the most attractive approaches for designing and developing anti-cancer drugs to avoid chemoresistance exhibited by clinically approved ATP-competitive inhibitors. The current work aimed to synthesize new biphenyl-containing derivatives that were predicted to act as EGFR TK allosteric site inhibitors based on molecular docking studies.

Methods:

A new series of 4'-hydroxybiphenyl-4-carboxylic acid derivatives, including hydrazine-1-carbothioamide (S3-S6) and 1,2,4-triazole (S7-S10) derivatives, were synthesized and characterized using IR, 1HNMR, 13CNMR, and HR-mass spectroscopy.

Results:

Compound S4 had a relatively high pharmacophore-fit score, indicating that it may have biological activity similar to the EGFR allosteric inhibitor reference, and it scored a relatively low ΔG against EGFR TK allosteric site, indicating a high likelihood of drug-receptor complex formation. Compound S4 was cytotoxic to the three cancer cell lines tested, particularly HCT-116 colorectal cancer cells, with an IC50 value comparable to Erlotinib. Compound S4 induced the intrinsic apoptotic pathway in HCT-116 cells by arresting them in the G2/M phase. All of the new derivatives, including S4, met the in silico requirements for EGFR allosteric inhibitory activity.

Conclusion:

Compound S4 is a promising EGFR tyrosine kinase allosteric inhibitor that warrants further research.

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Publication Date
Sat Apr 01 2023
Journal Name
Baghdad Science Journal
New sizes of complete (k, 4)-arcs in PG(2,17)
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              In this paper, the packing problem for complete (  4)-arcs in  is partially solved. The minimum and the maximum sizes of complete (  4)-arcs in  are obtained. The idea that has been used to do this classification is based on using the algorithm introduced in Section 3 in this paper. Also, this paper establishes the connection between the projective geometry in terms of a complete ( , 4)-arc in  and the algebraic characteristics of a plane quartic curve over the field  represented by the number of its rational points and inflexion points. In addition, some sizes of complete (  6)-arcs in the projective plane of order thirteen are established, namely for  = 53, 54, 55, 56.

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Publication Date
Thu Jun 25 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis and Preliminary Biological Activity Evaluation of New N- Substituted Phthalimide Derivatives
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A

A new series of bases of Schiff (H2-H4) derived from phthalic anhydrideweresynthesized. These Schiff bases were prepared by the reaction of different amines (tyrosine methyl ester, phenylalanine methyl ester, and isoniazid) with the phthalimide derived aldehyde with the aid of glacial acetic acid or triethylamine ascatalysts. All the synthesized compounds were characterized by (FT-IR and 1HNMR) analyses and were in vitro evaluated for their antimicrobial activity against six various kinds of microorganisms. All the synthesized compounds had been screened for their antimicrobial activity against two Gram-positive bacteria “Staph. Aureus, and Bacillus subtilis

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Publication Date
Sun Aug 01 2021
Journal Name
Nano Biomedicine And Engineering
In-vivo and In-vitro Anti-Acinetobacter Baumannii Activity of Citrate-Capped Silver Nanoparticles
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Silver nanoparticles (AgNPs) are of potential interest because of their effective antibacterial and antiviral activities. Capping agents are used for exhibiting a better antibacterial activity than uncapped Ag NPs. There are very few reports that have shown the usage of AgNPs for in-vivo antibacterial therapy. Citrate-capped silver nanoparticles were synthesized chemically by citrate reduction method; the size of Cit-AgNPs was determined by an atomic force microscope (AFM) and was between 15-90 nm. Acinetobacter baumannii (A. baumannii) isolates were the only sensitive species to Cit-AgNPs. MICs and MBC of Cit-AgNPs were determined by using A. baumannii. The results showed an additive effect of Cit-AgNPs. Four mice groups were infected with

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Publication Date
Fri Oct 24 2014
Journal Name
Journal Of Chemical And Pharmaceutical Research
Synthesis, characterization and antimicrobial activities of [Fe(II), Co(II), Ni(II),Cu(II) and Zn(II)] mixed ligand complexes schiff base derived from amoxicillin drug and 4-(dimethylamino)benzaldehyde with nicotinamide
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New Schiff base ligand (E)-6-(2-(4-(dimethylamino)benzylideneamino)-2-(4-hydroxyphenyl)acetamido)-3,3- dimethyl-7-oxo-4-thia-1- azabicyclo[3.2.0]heptane-2-carboxylic acid = (HL) was synthesized via condensation of Amoxicillin and 4(dimethylamino)benzaldehyde in methanol. Figure -1 Polydentate mixed ligand complexes were obtained from 1:1:2 molar ratio reactions with metal ions and HL, 2NA on reaction with MCl2 .nH2O salt yields complexes corresponding to the formulas [M(L)(NA)2Cl],where M=Fe(II),Co(II),Ni(II),Cu(II),and Zn(II), A=nicotinamide .

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Publication Date
Mon Feb 23 2026
Journal Name
Baghdad Science Journal
Synthesis, Spectroscopic Characterization, and Photostability Studies of a New Ligand Derivative of 4-Bromobenzaldehyde and its Metal Complexes
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Publication Date
Wed Sep 16 2020
Journal Name
Journal Of Chemistry
Synthesis of Phthalimide Imine Derivatives as a Potential Anticancer Agent
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The outstanding evidence of phthalimide pharmacophore in securing enhanced biological activities had encouraged further research and development into phthalimide-based derivatives as potential new drugs. In this study, phthalimide core was hybridized with aldehydes giving integrated imines displaying different types of functionalities and at alternating positions. The resulting compounds, therefore, provide an innovative window to explore possible differential biological effects as antioxidants and anticancer agents. A total of sixteen compounds were synthesized, and each was verified by FT-IR, H NMR, C NMR, and MS characterization. Herein, a facile single-step synthesis method was employed substituting the conventional two-step che

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Publication Date
Sun Mar 08 2020
Journal Name
Biochem. Cell. Arch
SYNTHESIS AND SPECTROSCOPIC CHARACTERIZATION OF NEW HETEROCYCLIC COMPOUNDS DERIVATIED FROM 1-(4-AMINOPHENYL) ETHAN-1-ONEOXIME AS A STARTING MATERIAL WITH EVALUATE THEIR BIOLOGICAL ACTIVITY
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ABSTRACT : This research involves the synthesis of five to seven heterocyclic compounds starting with Schiff’s bases which derived from oxime as a starting material. 1.3-oxazepine derivatives were prepared from adding different anhydrides to the Schiff bases, tetrazole and thiazolidinone derivatives synthesized from add sodium azide and thioglycolic acid to the same Schiff’s bases as a five members ring. Pyrimidine derivatives were prepared after the reaction of the azomethine group with acetyl chloride and then urea and thiourea to synthesis on derivatives contain the six members ring. Another step included identified and confirmed these compounds by FT- IR, 1HNMR, TLC and 13CNMR finally, step included the assay of biological activity

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Publication Date
Sun Sep 04 2016
Journal Name
Baghdad Science Journal
Synthesis and Characterization of Some New Pyrazoline and Isoxazoline Derivatives as Antibacterial Agents
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In this paper some chalcones (C1-C8) are prepared based on the reaction of one mole of substituted acetophenone with one mole of substituted benzaldehydes in the presence of (40%) sodium hydroxide as a base. Pyrazolines (P1–P8) are prepared from the reaction of chalcones (C1-C8) with hydrazine hydrate. Isoxazoline (I1-I8) is prepared from the reaction of chalcones (C1-C8) with hydroxyl amine hydrochloride in the presence of (10%) sodium hydroxide as a base. These compounds are characterized by using various physical and spectral methods. The compounds are screened for their in vitro antibacterial activity using gram-positive bacteria and gram-negative bacteria. Several derivatives of pyrazolines and isoxazolines are produced well to moder

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Publication Date
Sun Feb 10 2019
Journal Name
Drug Invention Today
Design, characterization, and in vitro evaluation of zaltoprofen solid dispersion as a hollow-type rectal suppository
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Aim: The present study aims to improve the poor water solubility of zaltoprofen which is a non-steroidal anti-inflammatory drug (NSAIDs) with a potent analgesic effect using solid dispersion then formulate it as a hollow type suppository to be more convenient for geriatric patients. Materials and Method: Zaltoprofen solid dispersions were prepared by solvent evaporation technique in different zaltoprofen: Soluplus® ratios. Results: Among the formulations tested, zaltoprofen solid dispersion preparation using 1:5 (zaltoprofen: Soluplus®) ratio showed the highest solubility and selected for further investigation. Solid dispersion characterization was evaluated by differential scanning calorimetry (DSC), X-ray diffraction study (XRD) and Fou

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Publication Date
Wed Mar 29 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Development and in vitro Evaluation of Bioadhesive Vaginal Tablet using Econazole Nitrate as a Model Drug
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         In this study, a bioadhesive dosage form of eoconazole nitrate for vaginal delivery was designed using a combination of bioadhesive polymers: Carbopol 941 p and sodium carboxymethylcellulose or methylcellulose in different ratios. The bioadhesive strength was evaluated by measuring the force required to detach the tablet from sheep vaginal mucosal membrane. It was found that the bioadhesive force was directly proportional to Carbopol 941 p content in the different formulae. The formulae were tested for their swelling behavior using agar gel plate method. The results showed that formulae containing a combination of Carbopol 941 p and sodium carboxymethylcellulose had greater swelling index

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