Synthesis and Evaluation of Marine-Inspired Compounds Result in Hybrids with Antitrypanosomal and Antileishmanial Activities.

Natural products are a very rich source for obtaining new compounds with therapeutic potential. In the search for new antiparasitic and antimicrobial agents, molecular hybrids were designed based on the structures of antimicrobial marine quinazolinones and eugenol, a natural phenolic compound. Following reports of the therapeutic potential of quinazolinones and eugenol derivatives, it was expected that the union of these pharmacophores could generate biologically relevant substances. The designed compounds were obtained by classical synthetic procedures and were characterized by routine spectrometric techniques. Nine intermediates and final products were then evaluated in vitro against Trypanosoma brucei and Leishmania infantum. Antifungal and antibacterial activity were also evaluated. Six compounds (9b, 9c, 9d, 10b, 10c, and 14) showed mild activity against T. brucei with IC50 in the range of 11.17-31.68 µM. Additionally, intermediate 9c showed anti-Leishmania activity (IC50 7.54 µM) and was six times less cytotoxic against THP-1 cells. In conclusion, novel derivatives with a simple quinazolinone scaffold showing selectivity against parasites without antibacterial and antifungal activities were disclosed, paving the way for new antitrypanosomal agents.

Design, Synthesis of Novel 1,2,3-Triazole Pendent Quinazolinones and Their Cytotoxicity against MCF-7 Cell Line.

A library of 6-(((1-(substitutedphenyl)-1H-1,2,3-triazol-4-yl)methyl) amino)-3-methylquinazolin-4(3H)-one analogues synthesized from Isatin precursor through a series of nitration, reduction, hydrolysis, cyclization and click reaction. The structures of compounds were characterized by spectral data including IR, 1 H-NMR, 13 C NMR and Mass. The novel quinazolinone - 1,2,3-triazoles were screened for their cytotoxicity against the human breast adenocarcinoma cell lines MCF-7 by MTT assay. 4-Isopropyl and 2-bromo substituted analogues executed high activity against MCF-7 cell line with IC50 value of 10.16±0.07 µM and 11.23±0.20 µM compared to the Doxorubicin whose IC50 value is 10.81±0.03 µM. The activity of remaining compounds is good to moderate. Further, the molecular docking studies against the crystal structure of Epidermal Growth Factor Receptor delivered the best binding energies and the interactions such as H-bond and hydrophobic are inevitable. The predicted pharmacokinetic properties results showed that these compounds have more drug likeness properties.

Design, synthesis and bioactivity evaluation of a series of quinazolinone derivatives as potent PI3Kγ antagonist.

Targeting PI3Kγ would be a useful strategy for treating inflammatory and cancer diseases. However, the development of selective inhibitors of PI3Kγ is very challenging due to the high structural and sequence homology with other PI3K isoforms. A series of quinazolinone derivatives were designed, synthesized and biologically evaluated as PI3Kγ-selective inhibitors. Among all the 28 compounds, compound 9b was found to be the most potent selective inhibitor with IC50 values of 13.11 nM against PI3Kγ kinase. Additionally, compound 9b could generate toxicity on leukemia cells in a panel of 12 different of cancer cell lines with the IC50 value of 2.41 ± 0.11 µM on Jurkat cell. Preliminary mechanism studies indicated that compound 9b through inhibit the activity of PI3K-AKT in human and murine leukemia cells, and activated phosphorylated p38 and phosphorylated ERK presented potent antiproliferative activity, which provided a potent small molecule for further cancer therapy.

Design, Synthesis and Antitumor Activity of FAK/PLK1 Dual Inhibitors with Quinazolinone as the Skeleton.

Febrifugine is a kind of quinazolinone compound with high biological activity from a Chinese herb called Chang Shan (Dichroa febrifuga). Febrifugine and its derivatives possess extensive biological activities, some of which exhibited anti-tumor activities as FAK inhibitors. However, they are not very effective at inhibiting tumor metastasis, perhaps because tumors gain energy through compensatory activation of other signaling pathways that promote cell migration and invasion. Therefore, seventeen novel febrifugine derivatives with quinazolinone skeleton were designed, synthesized and acted as potential FAK/PLK1 dual inhibitors. These compounds were determined by 1 H-NMR, 13 C-NMR and MS. Most of the compounds exhibited good inhibitory activity against cancer cell lines by computer-assisted screening, antitumor activity test and FAK/PLK1 inhibitory activity test, wherein compound 3b was screened as a high-efficiency lead compound.

Diversity oriented synthesis and SAR studies of new quinazolinones and related compounds as insecticidal agents against Culex pipiens L. Larvae and associated predator.

The ongoing study reports the synthesis, spectroscopic analyses and larvicidal efficacy of novel series of quinazolinone derivatives and related compounds. The structures of the products were confirmed relied on their analytical and spectral data (IR, 1H NMR, and 13C NMR). The spectral documentation promoted the successful isolation of the desirable compounds. The insecticidal activities of the synthesized compounds were assessed against laboratory and field strains of Culex pipiens larvae and a predator from the same ecological niche, Cybister tripunctatus. The results revealed that most of the tested compounds showed high potencies against lab strain of C. pipiens larvae with low resistance ratios in filed strain. In particular, compounds 15, 6 and 16 showed low LC50 values, 0.094, 0.106, 0.129 (µg/mL), respectively against lab strain of C. pipiens larvae. The present study also explored the toxicity of tested compounds against field strain of non-target C. tripunctatus. Most of tested compounds were safer than temephos, especially 15 and 6 with SI/PSF values 96.746 and 83.167, respectively. Structure-activity relationship (SAR) was discussed the effect of substituents insertion on the derivatives activities. Quinazolinone derivatives and related compounds are promising compounds in the mosquito control programs and further studies are recommended to develop more effective derivatives and reveal their mode of action.

Quinazolinones, the Winning Horse in Drug Discovery.

Quinazolines are nitrogen-containing heterocycles that consist of a benzene ring fused with a pyrimidine ring. Quinazolinones, oxidized quinazolines, are promising compounds with a wide range of biological activities. In the pharmaceutical field, quinazolinones are the building blocks of more than 150 naturally occurring alkaloids isolated from different plants, microorganisms, and animals. Scientists give a continuous interest in this moiety due to their stability and relatively easy methods for preparation. Their lipophilicity is another reason for this interest as it helps quinazolinones in penetration through the blood-brain barrier which makes them suitable for targeting different central nervous system diseases. Various modifications to the substitutions around the quinazolinone system changed their biological activity significantly due to changes in their physicochemical properties. Structure-activity relationship (SAR) studies of quinazolinone revealed that positions 2, 6, and 8 of the ring systems are significant for different pharmacological activities. In addition, it has been suggested that the addition of different heterocyclic moieties at position 3 could increase activity. In this review, we will highlight the chemical properties of quinazolinones, including their chemical reactions and different methods for their preparation. Moreover, we will try to modify some of the old SAR studies according to their updated biological activities in the last twelve years.

Nano-CuFe2O3-catalyzed green synthesis of novel quinazolinone-tetrazole hybrids as anti-cancer agents.

A novel green protocol has been developed for the synthesis of quinazolinone-tetrazole conjugates (7a-g, 8a-g and 9a-g) using recyclable nano-CuFe2O3 catalyst in water. Initially, 2-mercapto-3-substituted phenethylquinazolin-4(3H)-one (5a-c) was prepared by using nano-CuFe2O3 catalyst in water. Then, compounds (5a-c) were reacted with 1-bromo-3-chloropropane under nano-CuFe2O3 catalyst in water solvent to give S-alkylated quinazolinone core intermediate (6a-c), which was subsequently reacted with 1-substituted-1H-tetrazole-5-thiol (2a-g) by employing the similar reaction conditions to afford the final target compounds. The regioselective formation of C-S bond was unambiguously confirmed by single-crystal X-ray diffraction. The anti-cancer activity of the derivatives on various cancer cell lines such as SIHA, MD-AMB-231 and HepG2 was evaluated. Remarkably, compounds, 7f, 8f, 9a, 9d and 9f, showed potent activity in MD-AMB-231 cancer cell line (IC50: 9.13-10.3 µM), while the same derivatives showed significant potent activity in SiHa and HepG2 cancer cell lines (IC50: 17.46-27.0 µM). Most significantly, compound 7o (IC50: 8.15 µM) showed potent activity, compared to the drug etoposide (IC50: 18.11 µM) against MD-AMB-231 cell line. Flow cytometry analysis revealed that compounds 7f, 8f, 9a, 9d and 9f arrested the cell growth in the G1 phase in MD-AMB-231 cell line.

New quinazolinone-based derivatives as DHFR/EGFR-TK inhibitors: Synthesis, molecular modeling simulations, and anticancer activity.

New 2-mercapto-quinazolin-4-one analogs were synthesized and tested for their in vitro anticancer activity, dihydrofolate reductase (DHFR) inhibition, and epidermal growth factor tyrosine kinase (EGFR-TK) inhibition activities. Compound 24, which is characterized by a 2-benzyl-thio function, showed broad-spectrum anticancer activity with high safety profile and selectivity index. The concentrations of 24 causing 50% growth inhibition (GI50 ) and total cell growth inhibition (TGI) and its lethal concentration 50 (LC50 ) were 15.1, 52.5, and 91.2 µM, respectively, using 5-fluorouracil as a positive control. Also, it showed EGFR-TK inhibitory activity with IC50 = 13.40 nM compared to gefitinib (IC50 = 18.14 nM) and DHFR inhibitory potency with 0.30 µM compared to methotrexate (MTX; IC50 = 0.08 µM). In addition, compound 24 caused cell cycle arrest and apoptosis on COLO-205 colon cancer cells. Compounds 37, 21, and 54 showed remarkable DHFR inhibitory activity with IC50 values of 0.03, 0.08, and 0.08 µM, respectively. The inhibitory properties of these compounds are due to an electron-withdrawing group on the quinazolinone ring, except for compound 54. In a molecular modeling study, compound 24 showed the same binding mode as gefitinib as it interacted with the amino acid Lys745 via π-π interaction. Compound 37 showed a similar binding mode as MTX through the binding interaction with Lys68, Asn64 via hydrogen bond acceptor, and Phe31 via arene-arene interaction. The obtained model and substitution pattern could be used for further development.

Natural quinazolinones: From a treasure house to promising anticancer leads.

Despite great advances in the development of modern anticancer drugs, it is still challenging to find safer and more effective ones due to a new spectrum of diseases and emerging drug resistance. Natural quinazolinones exist widely in natural plants, microorganisms and animals and possess a variety of biological activities. Over the past three to four decades, there has been a growing volume of literature concerning the effects of natural quinazolinones and their derivatives upon a variety of cancers. In this paper, 58 natural quinazolinones with anticancer activities were reviewed in term of their anticancer effects, cellular and molecular mechanisms, ability to overcome cancer drug resistance, and structure-activity relationship of anticancer quinazolinone representatives as well. This paper will offer new clues for discovering new and better lead compounds against malignant tumor and cancer drug resistance from natural quinazolinones.

Synthesis of a Pyrrolo[1,2-a]quinazoline-1,5-dione Derivative by Mechanochemical Double Cyclocondensation Cascade.

N-heterocyclic compounds, such as quinazolinone derivatives, have significant biological activities. Nowadays, as the demand for environmentally benign, sustainable processes increases, the application of compounds from renewable sources, easily separable heterogeneous catalysts and efficient, alternative activation methods is of great importance. In this study, we have developed a convenient, green procedure for the preparation of 3a-methyl-2,3,3a,4-tetrahydropyrrolo[1,2-a]quinazoline-1,5-dione through a double cyclocondensation cascade using anthranilamide and ethyl levulinate. Screening of various heterogeneous Brønsted acid catalysts showed that Amberlyst® 15 is a convenient choice. By applying mechanochemical activation in the preparation of this N-heterotricyclic compound for the first time, it was possible to shorten the necessary time to three hours compared to the 24 h needed under conventional conditions to obtain a high yield of the target product.

Design, Synthesis and Antitumor Activities of Novel Quinazolinone Derivatives as Potential EGFR Inhibitors.

Human epidermal growth factor (EGFR) is an important target for antitumor drug research. A series of novel quinazolinone derivatives were synthesized and developed as potent inhibitors of EGFR. The results showed that most of the aimed compounds had potential anti-tumor cell proliferation activities. Some compounds were tested for their EGFR inhibitory activity. Especially, compound 6d showed the most potent antitumor activity with IC50 values of 1.58 µM against human breast cancer (MCF-7) cell lines and exhibited the most potent EGFR inhibitory activity with IC50 of 0.77 µM. Docking simulation was performed to position compound 6d into the EGFR active site to determine the probable binding conformation.

Accommodation of ring C expanded deoxyvasicinone in the HDAC inhibitory pharmacophore culminates into a tractable anti-lung cancer agent and pH-responsive nanocarrier.

A fragment recruitment process was conducted to pinpoint a suitable fragment for installation in the HDAC inhibitory template to furnish agents endowed with the potential to treat lung cancer. Resultantly, Ring C expanded deoxyvasicinone was selected as an appropriate surface recognition part that was accommodated in the HDAC three-component model. Delightfully, fused quinazolinone 6 demonstrating a magnificent anticancer profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80-0.96 µM) was identified. Results of the mechanistic studies confirmed that the cell growth inhibitory effects of compound 6 stems for HDAC6 (IC50 = 12.9 nM), HDAC1 (IC50 = 49.9 nM) and HDAC3 inhibition (IC50 = 68.5 nM), respectively. Compound 6 also suppressed the colony formation ability of A549 cells, induced apoptosis, and increased autophagic flux. Key interactions of HDAC inhibitor 6 within the active site of HDAC isoforms were figured out through molecular modeling studies. Furthermore, a pH-responsive nanocarrier (Hyaluronic acid - fused quinazolinone 6 nanoparticles) was designed and assessed using a dialysis bag approach under both normal and acidic circumstances that confirmed the pH-sensitive nature of NPs. Delightfully, the nanoparticles demonstrated selective cell viability reduction potential towards the lung cancer cell lines (A549 lung cancer cell lines) and were found to be largely devoid of cell growth inhibitory effects under normal settings (L929, mouse fibroblast cells).

Recent advances in the synthesis of 2,3-fused quinazolinones.

As one of the most important structural units in pharmaceuticals and medicinal chemistry, quinazolinone and its derivatives exhibit a wide range of biological and pharmacological activities, including anti-inflammatory, antitubercular, antiviral, and anticancer activities, etc. In particular, 2,3-fused quinazolinones have attracted much attention because the rings fused to the 2,3-positions of quinazolinones improve their rigidity and planarity. Their synthetic strategies have made great advances in recent years. Therefore, this review focuses on novel strategies for the synthesis of 2,3-fused quinazolinone derivatives from 2017 to 2022, such as the difunctionalization of alkenes, the ring-opening of easily available small rings, dehydrogenative cross-coupling reactions, transition-metal catalyzed cyclizations, cycloadditions, and other cascade reactions.

Design, Synthesis and Molecular Docking of Novel Quinazolinone Hydrazide Derivatives as EGFR Inhibitors.

A series of novel quinazolinone hydrazide derivatives were designed and synthesized as EGFR inhibitors. The results indicated that most of the aimed compounds had potential anti-tumor cell proliferation and EGFR inhibitory activities. In the comprehensive analysis of all the tested compounds, the target compound 9c showed the best anti-tumor cell proliferation activity, (IC50 =1.31 µM for MCF-7, IC50 =1.89 µM for HepG2, IC50 =2.10 µM for SGC), and IC50 =0.59 µM for the EGFR inhibitory activity. Docking results showed that compound 9c could ideally insert the active site and interact with the critical amino acid residues (Val702, Lys721, Met769, Asp831) in the active site.

In Silico and In Vitro Evaluations of Fluorophoric Thiazolo-[2,3-b]quinazolinones as Anti-cancer Agents Targeting EGFR-TKD.

Epidermal growth factor receptor tyrosine kinase domain (EGFR-TKD) plays a pivotal role in cellular signaling, growth, and metabolism. The EGFR-TKD is highly expressed in cancer cells and was endorsed as a therapeutic target for cancer management to overcome metastasis, cell proliferation, and angiogenesis. The novel thiazolo-[2,3-b]quinazolinones series were strategically developed by microwave-assisted organic synthesis and multi dominos reactions aimed to identify the potent thiazolo-[2,3-b]quinazolinone inhibitor against EGFR-TKD. This study explores the binding stability and binding strength of newly developed series via molecular docking, molecular dynamics simulation, and MM/PBSA and MM/GBSA calculations. The binding interaction was observed to be through the functional groups on aryl substituents at positions 3 and 5 of the thiazolo-[2, 3-b]quinazolinone scaffold. The methyl substituents at position 8 of the ligands had prominent hydrophobic interactions corroborating their bindings similar to the reference FDA-approved drug erlotinib in the active site. ADMET predictions reveal that derivatives 5ab, 5aq, and 5bq are drug-like and may be effective in in vitro study. Molecular dynamics simulation for 100 ns of docked complexes revealed their stability at the atomistic level. The ΔGbinding of thiazolo-[2,3-b]quinazolinone was found to be 5ab - 22.45, 5aq - 22.23, and 5bq - 20.76 similar to standard drug, and erlotinib - 24.11 kcal/mol was determined by MM/GBSA method. Furthermore, the anti-proliferative activity of leads of thiazolo-[2,3-b]quinazolinones (n = 3) was studied against breast cancer cell line (MCF-7) and non-small lung carcinoma cell line (H-1299). The highest inhibitions in cell proliferation were shown by 5bq derivatives, and the IC50 was found to be 6.5 ± 0.67 µM against MCF-7 and 14.8 µM against H-1299. The noscapine was also taken as a positive control and showed IC50 at higher concentrations 37 ± 1 against MCF-7 and 46.5 ± 1.2 against H-1299.

Potential anti-acanthamoebic effects through inhibition of CYP51 by novel quinazolinones.

Acanthamoeba spp. are free living amoebae which can give rise to Acanthamoeba keratitis and granulomatous amoebic encephalitis. The surface of Acanthamoeba contains ergosterol which is an important target for drug development against eukaryotic microorganisms. A library of ten functionally diverse quinazolinone derivatives (Q1-Q10) were synthesised to assess their activity against Acanthamoeba castellanii T4. The in-vitro effectiveness of these quinazolinones were investigated against Acanthamoeba castellanii by amoebicidal, excystation, host cell cytopathogenicity, and NADPH-cytochrome c reductase assays. Furthermore, wound healing capability was assessed at different time durations. Maximum inhibition at 50 µg/mL was recorded for compounds Q5, Q6 and Q8, while the compound Q3 did not exhibit amoebicidal effects at tested concentrations. Moreover, LDH assay was conducted to assess the cytotoxicity of quinazolinones against HaCaT cell line. The results of wound healing assay revealed that all compounds are not cytotoxic and are likely to promote wound healing at 10 µg/mL. The excystation assays revealed that these compounds significantly inhibit the morphological transformation of A. castellanii. Compound Q3, Q7 and Q8 elevated the level of NADPH-cytochrome c reductase up to five folds. Sterol 14alpha-demethylase (CYP51) a reference enzyme in ergosterol pathway was used as a potential target for anti-amoebic drugs. In this study using i-Tasser, the protein structure of Acanthamoeba castellanii (AcCYP51) was developed in comparison with Naegleria fowleri protein (NfCYP51) structure. The sequence alignment of both proteins has shown 42.72% identity. Compounds Q1-Q10 were then molecularly docked with the predicted AcCYP51. Out of ten quinazolinones, three compounds (Q3, Q7 and Q8) showed good binding activity within 3 Å of TYR 114. The in-silico study confirmed that these compounds are the inhibitor of CYP51 target site. This report presents several potential lead compounds belonging to quinazolinone derivatives for drug discovery against Acanthamoeba infections.

Development of newly synthesised quinazolinone-based CDK2 inhibitors with potent efficacy against melanoma.

Inhibiting Cyclin-dependent kinase 2 (CDK2) has been established as a therapeutic strategy for the treatment of many cancers. Accordingly, this study aimed at developing a new set of quinazolinone-based derivatives as CDK2 inhibitors. The new compounds were evaluated for their anticancer activity against sixty tumour cell lines. Compounds 5c and 8a showed excellent growth inhibition against the melanoma cell line MDA-MB-435 with GI% of 94.53 and 94.15, respectively. Cell cycle analysis showed that compound 5c led to cell cycle cessation at S phase and G2/M phase revealing that CDK2 could be the plausible biological target. Thus, the most cytotoxic candidates 5c and 8a were evaluated in vitro for their CDK2 inhibitory activity and were able to display significant inhibitory action. The molecular docking study confirmed the obtained results. ADME study predicted that 5c had appropriate drug-likeness properties. These findings highlight a rationale for further development and optimisation of novel CDK2 inhibitors.

Design and synthesis of novel nitrothiazolacetamide conjugated to different thioquinazolinone derivatives as anti-urease agents.

The present article describes the design, synthesis, in vitro urease inhibition, and in silico molecular docking studies of a novel series of nitrothiazolacetamide conjugated to different thioquinazolinones. Fourteen nitrothiazolacetamide bearing thioquinazolinones derivatives (8a-n) were synthesized through the reaction of isatoic anhydride with different amine, followed by reaction with carbon disulfide and KOH in ethanol. The intermediates were then converted into final products by treating them with 2-chloro-N-(5-nitrothiazol-2-yl)acetamide in DMF. All derivatives were then characterized through different spectroscopic techniques (1H, 13C-NMR, MS, and FTIR). In vitro screening of these molecules against urease demonstrated the potent urease inhibitory potential of derivatives with IC50 values ranging between 2.22 ± 0.09 and 8.43 ± 0.61 µM when compared with the standard thiourea (IC50 = 22.50 ± 0.44 µM). Compound 8h as the most potent derivative exhibited an uncompetitive inhibition pattern against urease in the kinetic study. The high anti-ureolytic activity of 8h was confirmed against two urease-positive microorganisms. According to molecular docking study, 8h exhibited several hydrophobic interactions with Lys10, Leu11, Met44, Ala47, Ala85, Phe87, and Pro88 residues plus two hydrogen bound interactions with Thr86. According to the in silico assessment, the ADME-Toxicity and drug-likeness profile of synthesized compounds were in the acceptable range.

Design and synthesis of novel quinazolinone derivatives as anti-HBV agents with TLR8 agonist effect.

Hepatitis B virus (HBV) infection is a worldwide threat to public health. In this work, a series of novel quinazolinone derivatives (5a-q) were synthesized and evaluated as novel anti-HBV agents. Among them, compound 5l exhibited potent inhibitory effect on HBV DNA replication in both wild type and drug resistant (lamivudine and entecavir) HBV strains with IC50 values of 0.15 and 0.10 µM, respectively. Notably, the selective index value of 5l was high above 66.67, indicating the favorable safety profile. Molecular docking study indicated that compound 5l well fitted into the binding pocket of TLR8 protein-protein interface. Dual-luciferase reporter gene assay further confirmed that compound 5l could dose-dependently activate TLR8, thus effectively inducing the activity of TLR8-dependent NF-κB. Collectively, compound 5l displayed potent anti-HBV activities and TLR8 agonist effect in vitro, and might be a potential immunomodulatory anti-HBV agent to warrant further investigation.

Synthesis, X-ray Structure, Hirshfeld, DFT and Biological Studies on a Quinazolinone-Nitrate Complex.

The reaction of 4-hydroxyquinazoline (4HQZ) with aqueous solution of nitric acid afforded the corresponding quinazolinone-nitrate (4HQZN) complex in very good yield. The crystal structure of 4HQZN was determined and its structural and supramolecular structural aspects were analyzed. 4HQZN crystallized in the space group P21/c and monoclinic crystal system with one [4HQZ-H]+[NO3]- formula and Z = 4. Its supramolecular structure could be described as a 2D infinite layers in which the 4HQZN molecules are connected via N-H…O and C-H…O hydrogen bridges. Using DFT calculations, the relative stability of five suggested isomers of 4HQZN were predicted. It was found that the medium effects have strong impact not only on the isomers' stability but also on the structure of the 4HQZN. It was found that the structure of 4HQZN in DMSO and methanol matched well with the reported X-ray structure which shed the light on the importance of the intermolecular interactions on the isomers' stability. The structure of 4HQZN could be described as a proton transfer complex in which the nitrate anion acting as an e-donor whiles the protonated 4HQZ is an e-acceptor. In contrast, the structure of the isolated 4HQZN in gas phase and in cyclohexane could be described as a 4HQZ…HNO3 hydrogen bonded complex. Biological screening of the antioxidant, anticancer and antimicrobial activities of 4HQZ and 4HQZN was presented and compared. It was found that, 4HQZN has higher antioxidant activity (IC50 = 36.59 ± 1.23 µg/mL) than 4HQZ. Both of 4HQZ and 4HQZN showed cell growth inhibition against breast (MCF-7) and lung (A-549) carcinoma cell lines with different extents. The 4HQZ has better activity with IC50 of 178.08 ± 6.24 µg/mL and 119.84 ± 4.98 µg/mL, respectively. The corresponding values for 4HQZN are 249.87 ± 9.71 µg/mL and 237.02 ± 8.64 µg/mL, respectively. Also, the antibacterial and antifungal activities of 4HQZN are higher than 4HQZ against all studied microbes. The most promising result is for 4HQZN against A. fumigatus (MIC = 312.5 µg/mL).