Quinoline Derivatives Research Articles

Potassium Phosphate-Mediated Synthesis of C4-Phosphorylated Quinolines via Cascade Cycloisomerization of Ynones.

A cascade phosphorylation cycloisomerization of readily accessible ynones and diphenylphosphine oxides facilitated by potassium phosphate is described, allowing for the straightforward synthesis of C4-phosphorylated quinoline scaffolds. The formation of a C-P bond and a C-N bond is achieved in a single procedure without the need for pre-assembled quinoline cores prior to phosphorylation. This transformation operates without the requirement for metals or oxidants and exhibits excellent compatibility with various functional groups. Furthermore, antimicrobial activity evaluation demonstrated that the synthesized C4 phosphorylated quinoline derivatives exhibited potent inhibitory activity against Staphylococcus aureus.

Absorption, Fluorescence, and Two-Photon Excitation Ability of 5-o-Tolyl-11 (or 13)-o-tolylisoindolo[2,1-a]quinolines Prepared by Ring-Closing Metathesis and [2+3] Cycloaddition.

We have successfully improved the fluorescence quantum yield of isoindolo[2,1-a]quinoline derivatives by suppressing the rotation of the phenyl groups at positions 5 and 11 (or 13). Additionally, we found that the planarity of these phenyl groups at positions 5 and 13 of isoindolo[2,1-a]quinoline derivatives is crucial for two-photon absorption properties.

Chemistry and Biological Activity of Thieno[3,4-b]quinoline, Thieno[3,4-c] quinolone, Thieno[3,2-g]quinoline and Thieno[2,3-g]quinoline Derivatives: A Review (Part IX)

Abstract: Over the previous decades, thieno-quinoline derivatives have acquired great interest due to their synthetic and biological applications. These reports have been disclosed on Thienoquinoline synthesis such as thieno[3,4-b]quinoline; thieno[3,4-c]quinolone; thieno [3,2-g]quinoline; thieno[2,3- g] quinoline; spiro-thieno[2,3-g]quinoline; benzo[b]thiophen-iso- quinoline derivatives, and therefore in the existent review, we provided an inclusive update on the synthesis of thienoquinolines. Characterization of the preparation methods and reactivity is categorized based on their types of reactions as addition, alkylation, chlorination, acylation, oxidation, reduction, cyclization and cyclo-condensation. Hence, this study will help the researchers to obtain knowledge from the last literature research to conquer their resolve problems in designing new compounds and processes.

Recent Progress in Synthetic Chemistry and Biological Activities of Pyrimido[ 4,5-b] Quinoline Derivatives (Part III)

Abstract: Amongst heterocyclic compounds, quinoline and pyrimidine are advantaged scaffolds that appear as significant assembly motifs for the development of new drug entities. Moreover, quinolinepyrimidine- inspired hybrids have a number of biological characteristics that are known. In addition, many pyrimido[4,5-b]quinoline ring systems (PyQs4,5-b), specifically concerning medicinal chemistry, have been reported over the past decade. The synthesis of (PyQs4,5-b) using barbituric acid, thiobarbituric acid, pyrimidine, and their derivatives is presented in this review. The preparation of PyQs4,5-b was clarified through the following chemical reactions: Friedländer, Vilsmeier-Haack formylation, Hantzsch-like reaction, and one-pot three-component reaction.

Quinoline as a Privileged Structure: A Recent Update on Synthesis and Biological Activities.

Among heterocyclic compounds, quinoline is one of the best ubiquitous heterocyclic rings for medicinal chemistry purposes. Quinoline appears to be a powerful chemical structure to develop new drug entities. The quinoline derivatives own a wide array of biological activities such as anticancer, antimalarial, antimicrobial, anti-inflammatory, anti-leishmanial, etc. Because of the wide spectrum of bioactivities, the scientific communities are still looking for more efficient synthetic routes to form quinoline derivatives. Therefore, the primary focus of this review is to provide a thorough and inclusive, updated report on quinoline analogs that may pave the way for more efficient drug development.

Design and Synthesis of Ester Linked 1,2,3‐Triazole Quinoline Derivatives with Pancreatic β Cells Protective Activity against Oxidative Stress and Endoplasmic Reticulum Stress for Better Management of Type II Diabetes Mellitus

AbstractUnresolved endoplasmic reticulum (ER) stress and oxidative stress lead to the pathogenesis of type II diabetes mellitus (DM). Connecting links between the ER stress and oxidative stress pathways might play an important role in treatment and pathogenesis of diabetes. Here, we used network pharmacology approach to find the target proteins linking the ER stress and oxidative stress pathways. CHOP emerged as a hub protein from our results and was targeted by 16 newly designed and synthesized ester linked 1,2,3‐triazole quinoline derivatives by molecular docking. Drug likeliness prediction studies revealed all compounds as good druggable candidates. Compounds 5b (R = H, R1 = F), 5j (R = CH3, R1 = F), 5m (R = OCH3, R1 = H), and 5n (R = OCH3, R1 = F) were found to have considerable binding energies and active site amino acid interactions with CHOP. We further showed that compounds 5b, 5m, and 5n exhibited low toxicity with more than 50% cell survival and low IC50 values. These were therefore subjected to evaluate their effects on ER stress and oxidative stress. Finally, compound 5n (R = OCH3, R1 = F) was found to alleviate ER stress and is also a good antioxidant. Identification of such targets and compounds effective in improving ER stress and oxidative stress may provide new insights in the development of therapies and management of T2DM.

A Novel Synthesis Route of Phenyl Quinoline from Nitrochalcone with Hydrazine Hydrate in the Presence of Pd/C

Quinoline is widely known to have many biological activities. Therefore, the development of the synthesis method of a quinoline derivative framework is a priority. A phenyl quinoline derivative, 6,7-dimethoxy-2-phenylquinoline Q1, has been successfully synthesized via a novel one-pot reaction that involves reduction, cyclization, and followed by dehydration of nitrochalcone derivate, 3-(4,5-dimethoxy-2-nitrophenyl)-1-phenylprop-2-en-1-one C1. The reaction was carried out using 80 % hydrazine hydrate in the presence of 10% Pd/C as a catalyst in an ethanol medium. Target compound Q1 was afforded in a good yield of 69.18% in a relatively short reaction time of ±2 h.

Solvent Choice during Flow Assembly of Photocross-Linked Single-Chain Nanoparticles and Micelles Affects Cellular Uptake.

Polymeric micelles have widely been used as drug delivery carriers, and recently, single-chain nanoparticles (SCNPs) emerged as potential, smaller-sized, alternatives. In this work, we are comparing both NPs side by side and evaluate their ability to be internalized by breast cancer cells (MCF-7) and macrophages (RAW 264.7). To be able to generate these NPs on demand, the polymers were assembled by flow, followed by the stabilization of the structures by photocross-linking using blue light. The central aim of this work is to evaluate how the type of solvent affects self-assembly and ultimately the structure of the final NP. Therefore, a library of copolymers with different sequences, including block copolymers (AB, ABA, BAB), and statistical copolymers (rAB and rAC) was synthesized using PET-RAFT with A denoting poly(ethylene glycol) methyl ether acrylate (PEGMEA), B as 2-hydroxyethyl acrylate (HEA), and C as 4-hydroxybutyl acrylate (HBA). The polymers were conjugated with a quinoline derivative to enable the formation of cross-linked structures by photocross-linking during flow assembly. Using water as the dispersant for photocross-linking led to the preassembly of these amphiphilic polymers into compact SCNPs and cross-linked micelles, resulting in a quick photoreaction. In contrast, acetonitrile led to fully dissolved polymers but a low rate of the photoreaction. These intramolecularly cross-linked polymers were then placed in water to result in more dynamic micelles and looser SCNPs. Small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), and size exclusion chromatography (SEC) coupled with a viscosity detector show that cross-linking in acetonitrile results in better-defined NPs with a shell rich in PEGMEA. Cross-linking in acetonitrile led to NPs with significantly higher cellular uptake. Interestingly, passive transport was identified as the main pathway for the delivery of our NPs on MCF-7 cells, confirmed by the uptake of NPs on cells treated with inhibitors and by red blood cells. This work underscored the importance of the polymer precursor's structure and the choice of solvent during intramolecular cross-linking in determining the drug delivery efficiency and biological behavior of SCNPs.

Pd-Catalyzed Dual C-H Activation/Cyclization: Convergent and Divergent Synthesis of 1-Azahelicenes.

Herein, we report a convergent synthesis of 1-azahelicenes using easily available quinoline derivatives and cyclic diaryliodonium salts as starting materials. This reaction undergoes a palladium-catalyzed dual C-H activation/cyclization process to give facile access to a wide range of 1-aza[5]helicenes and 1-aza[6]helicenes with abundant functional groups (including F, Cl, Br, I, CF3, SeR, SR, and heteroaryl) in moderate to excellent yields, thereby providing new opportunities to fine-tune the properties of the helicene backbone. In addition, the obtained products could be further transformed into helicene-based Lewis base catalysts and redox switch materials easily. Notably, one selected 1-azahelicene shined bright yellow light by aggregation. These features enlarge the chemical space of 1-azahelicenes and inspire further utilization in other areas of research.

Quinoline Synthesis: Nanocatalyzed Green Protocols-An Overview.

Heterocyclic compounds are of great interest in our daily lives. They are widely distributed in nature and are synthesized in laboratories. Heterocycles play an important role in the metabolism of all living cells, including vitamins and coenzyme precursors like thiamine and riboflavin. Furthermore, heterocyclic systems are essential building blocks for creating innovative materials with intriguing electrical, mechanical, and biological properties. Also, more than 85% of all biologically active chemical entities comprise a heterocycle. As a result, heterocycle synthesis piqued researchers' curiosity, and in recent decades, chemists have concentrated more on nitrogen-containing cyclic nuclei in structures. Quinoline and its derivatives exhibit several biological functions, including antimicrobial, anticancer, antimalarial, anti-inflammatory, antihypertensive, and antiasthmatic effects. In addition, over a hundred quinoline-based drugs are available to treat a variety of disorders. Because of its biological importance, researchers developed one-pot synthetic methods employing effective acid/base catalysts (Lewis acids, Brønsted acids, and ionic liquids), reagents, and transition-metal-based catalysts. These methods have some downsides, including longer reaction times, harsher reaction conditions, creation of byproducts, costly catalysts, use of hazardous solvents, an unacceptable economic yield, and catalyst recovery. Researchers' focus has switched to creating environmentally friendly and effective methods for the synthesis of quinoline derivatives as a result of these methodologic shortcomings. Because of its special qualities, the use of nanocatalysts or nanocomposites offers an option for the effective synthesis of quinolines. This review focuses on the published research articles on nanocatalysts to synthesize substituted quinoline derivatives. This review covers all contributions until May 2024, focusing on quinoline ring building and mechanistic issues. With the aid of this review, we anticipate that synthetic chemists will be able to develop more effective methods of synthesizing quinolines.

Gold‐catalyzed Annulation between 1‐[2‐(Dimethoxymethyl)phenyl]prop‐2‐yn‐1‐yl Acetates and α‐Diazoesters or Anilines to Form Substituted Naphthoates and Indeno[1,2‐b]quinoline, Respectively.

This work describes gold‐catalyzed annulations of 1‐(2‐(dimethoxymethyl)phenyl)‐1‐prop‐2‐yn‐1‐yl acetate substrates with α‐diazo esters and anilines, respectively yielding substituted naphthoates and indeno[1,2‐b]quinoline derivatives. Our mechanistic analysis indicates 1‐methoxy‐2‐carbonyl‐1H‐indenes as their common intermediates. In the formation of naphthoates, α‐diazo ester attacks at gold‐bound intermediate via a SN2 pathway to enable a allylic methoxy substitution. For indeno[1,2‐b]quinoline derivatives, there are two main reactions, including (i) a reversible formation between intermediate and a double amine addition product and (ii) an arylation reaction of intermediate. Species N‐(phenyl((2E)‐1‐(phenylimino)‐1,3‐dihydro‐2H‐inden‐2‐ylidene)methyl)aniline was converted to indeno[1,2‐b]quinoline in the presence of gold catalyst.

Catalytic N-Alkylation of (Hetero)Aromatic Amines and Tandem Annulation Reactions.

A general and practical approach for N-alkylation of heteroaromatic amines with heteroaromatic alcohols is always challenging and rarely reported. Here, we designed and synthesized phosphine-free, robust, and efficient N,N-bidentate-Co(II) complexes for a universal N-alkylation of amines strategy. This present catalytic methodology can be applied to a wide range of substrates by varying alcohols, including aryl, aliphatic, acyclic, and cyclic groups, with heteroaromatic amines such as aminopyridine, 2-aminopyrimidine, and aminoquinoline to provide diverse monoalkylated organonitrogen compounds in good to excellent yields (108 examples). In addition, the utility of the developed catalytic protocol was also extended successfully for the dehydrogenative synthesis of biologically important quinoline derivatives (11 examples). Particularly, 8-aminoquinoline reacted differently with tandem N-alkylated-transfer hydrogenative byproduct (N-benzyl-1,2,3,4-tetrahydroquinolin-8-amine) was obtained, revealing the catalytic activity of the complex I. The reaction proceeded under environmentally benign conditions, which liberates water as the sole byproduct. Notably, a concise synthesis of acetylcholinesterase inhibitors (AChEIs) scaffolds as potential cognition enhancers illustrated the utility of the present protocol. Interestingly, various control and deuterium-labeled experiments were performed, suggesting that the reaction proceeds via the borrowing hydrogen pathway.

Design, Synthesis, and Biological Evaluation of Novel Quinoline Derivatives against Phytopathogenic Bacteria Inspired from Natural Quinine Alkaloids.

A series of 2-(trifluoromethyl)-4-hydroxyquinoline derivatives were designed and synthesized with introduction of the antibacterial fragment amino alcohols, and their antibacterial activity against plant phytopathogenic bacteria was evaluated for the development of quinoline bactericides. It is worth noting that compound Qa5 exhibited excellent antibacterial activity in vitro with a minimum inhibitory concentration (MIC) value of 3.12 μg/mL against Xanthomonas oryzae (Xoo). Furthermore, in vivo assays demonstrated that the protective efficacy of Qa5 against rice bacterial blight at 200 μg/mL (33.0%) was superior to that of the commercial agent bismerthiazol (18.3%), while the curative efficacy (35.0%) was comparable to that of bismerthiazol (35.7%). The antibacterial mechanisms of Qa5 indicated that it affected the activity of bacteria by inducing intracellular oxidative damage in Xoo and disrupting the integrity of the bacterial cell membrane. The above results demonstrated that the novel quinoline derivative Qa5 possessed excellent in vitro and in vivo antibacterial activity, indicating its potential as a novel green agricultural antibacterial agent.

Evaluation of Quinoline-Related Carboxylic Acid Derivatives as Prospective Differentially Antiproliferative, Antioxidative, and Anti-Inflammatory Agents.

The higher prevalence of cancer and the unmet need for antioxidant/anti-inflammatory chemotherapeutic compounds with little side effect are of utmost importance. In addition, the increased likelihood of failure in clinical trials along with increasing development costs may have diminished the range of choices among newer drugs for clinical use. This has dictated the necessity to seek out novel medications by repurposing as it needs less time, effort, and resources to explore new uses of a current or unsuccessful medication. In this study, we examined the biological activity of 10 potential quinoline derivatives. Given the half-maximal inhibitory concentration (IC50 value) in lipopolysaccharide (LPS) induced inflammation of RAW264.7 mouse macrophages, all commercial FQs and selected quinolines (quinoline-4-carboxlic and quinoline-3-carboxylic acids) exerted impressively appreciable anti-inflammation affinities versus classical NSAID indomethacin without related cytotoxicities in inflamed macrophages. Conversely, all 14 tested compounds lacked antioxidative DPPH radical scavenging capacities as compared to ascorbic acid. Gemifloxacin, considerably unlike markets FQs, indomethacin and quinoline derivatives, exerted exceptional and differential antiproliferation propensities in colorectum SW480, HCT116, and CACO2, pancreatic PANC1, prostate PC3, mammary T47D, lung A375, and melanoma A549 adherent monolayers using the sulforhodamine B colorimetric method versus antineoplastic cisplatin. All quinoline derivatives and gemifloxacin alike, but not levofloxacin, ciprofloxacin, or indomethacin, displayed substantially selective viability reduction affinities in prolonged tumor incubations of cervical HELA and mammary MCF7 cells. Specifically kynurenic acid (hydrate), quinoline-2-carboxylic acid, quinoline-4-carboxylic acid, quinoline-3-carboxylic acid, and 1,2-dihydro-2-oxo-4-quinoline carboxylic acids possessed the most remarkable growth inhibition capacities against mammary MCF7 cell line, while quinoline-2-carboxylic acid was the only quinoline derivative with significant cytotoxicity on cervical HELA cancer cells. It is highly speculated that chelation with divalent metals via co-planarity with close proximity of the COOH and the N atom could have the potential molecular mechanism for optimally promising repurposed pharmacologies. Conclusively, this study revealed the considerably profound repurposed duality of cytotoxicity and anti-inflammation pharmacologies of quinoline derivatives. Activity-guided structural modifications of the present nuclear scaffolds can be inherently linked to the betterment and enhancement of their repurposed pharmacologies.

Exploring the adsorption characteristics of quinoline derivatives on iron via ab initio DFT simulations and COSMO-RS profiles

Quinoline derivatives have been the subject of extensive research due to their excellent electronic properties and wide range of applications. This study conducts a comprehensive computational examination of the adsorption properties of substituted quinoline derivatives on Fe(110) surfaces. Four specific compounds, namely 2-amino-7-hydroxy-4-phenyl-1,4-dihydroquinoline-3-carbonitrile (QN1), 2-amino-7-hydroxy-4-(p-tolyl)-1,4-dihydroquinoline-3-carbonitrile (QN2), 2-amino-7-hydroxy-4-(4-methoxyphenyl)-1,4-dihydroquinoline-3-carbonitrile (QN3), and 2-amino-4-(4-(dimethylamino)phenyl)-7-hydroxy-1,4-dihydroquinoline-3-carbonitrile (QN4) were investigated using first-principles density functional theory (DFT) calculations along with COSMO-RS analysis for solvation properties. Our results revealed that the presence of functional groups significantly influence the adsorption strength on Fe(110) surfaces. Quinoline molecules have adsorbed on the iron surface through complex mechanisms involving physical interactions and charge transfer. Specifically, QN1 and QN4 showed strong physical interactions with iron atoms while QN2 and QN3 exhibited high affinity to coordinate with Fe atoms. The stability of coordinated quinolines was enhanced by a notable charge redistribution and bond formation as observed via projected density of states (PDOS). On the other hand, electron density difference (EDD) and electron localization function (ELF) iso-surfaces highlighted the critical role of van der Waals interactions, predominantly influenced by nitrogen atoms, in stabilizing the adsorbed molecules. The COSMO-RS analysis elucidated the solvation characteristics, emphasizing the importance of hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) in the interaction of quinolines with water molecules. Overall, this study provides crucial insights into the molecular mechanisms underlying the corrosion inhibition properties of quinoline derivatives, emphasizing the influence of functional groups and solvation effects on adsorption behavior and stability.

Identifying Highly Active and Selective Cobalt X-Ides for Electrocatalytic Hydrogenation of Quinoline.

Earth-abundant Co X-ides are emerging as promising catalysts for the electrocatalytic hydrogenation of quinoline (ECHQ), yet challenging due to the limited fundamental understanding of ECHQ mechanism on Co X-ides. This work identifies the catalytic performance differences of Co X-ides in ECHQ and provides significant insights into the catalytic mechanism of ECHQ. Among selected Co X-ides, the Co3O4 presents the best ECHQ performance with a high conversion of 98.2% and 100% selectivity at ambient conditions. The Co3O4 sites present a higher proportion of 2-coordinated hydrogen-bonded water at the interface than other Co X-ides at a low negative potential, which enhances the kinetics of subsequent water dissociation to produce H*. An ideal 1,4/2,3-H* addition pathway on Co3O4 surface with a spontaneous desorption of 1,2,3,4-tetrahydroquinoline is demonstrated through operando tracing and theoretical calculations. In comparison, the Co9S8 sites display the lowest ECHQ performance due to the high thermodynamic barrier in the H* formation step, which suppresses subsequent hydrogenation; while the ECHQ on Co(OH)F and CoP sites undergo the 1,2,3,4- and 4,3/1,2-H* addition pathway respectively with the high desorption barriers and thus low conversion of quinoline. Moreover, the Co3O4 presents a wide substrate scope and allows excellent conversion of other quinoline derivatives and N-heterocyclic substrates.

Synthesis, characterization, antibacterial, antioxidant and molecular docking studies of Zn(II) complexes with imine quinoline derivative ligand

The efficacy of metal complexes with bioactive ligands for pharmaceutical purposes is increasingly gaining clinical and commercial importance for treating infectious diseases. This research aimed to synthesize new Zn(II) complexes, assess their potential applications in antibacterial and antioxidant properties, and explore their molecular docking properties. The synthesis was done by condensing 7-chloro-2-hydroxyquinoline-3-carbaldehyde and 2,2′-thiodianiline with Zn(II) metal complexes. A range of spectroscopic techniques, such as 1H and 13C NMR, FTIR, TG/DTA, pXRD, and UV–Vis, were employed to characterize both the ligand and its complexes. Imine quinoline ligand (L), ZnL, and ZnL2 all had average crystallite diameters of 13.28, 21.19, and 16.26 nm, respectively, according to pXRD analysis, which confirmed that the synthesized ligand and its Zn(II) complexes showed polycrystalline properties. Based on the results, an octahedral geometry was proposed for the complexes. A very good agreement was obtained between the experimental and the TD-DFT calculated absorption peaks. Their biological potency against Gram-positive (Staphylococcus aureus ATCC 25926) and Gram-negative (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 248) bacterial strains as well as antioxidant properties were tested. The ZnL complex showed a maximum growth inhibition of 9.50 ± 0.41 mm against S. aureus ATCC 25926; whereas the maximum growth inhibition of the ZnL2 complex was 9.67 ± 0.47 mm and 9.33 ± 0.47 mm against ATCC 25926, respectively. With an IC50 of 167.3 ± 1.04 mg/mL, ZnL had the strongest antioxidant activity against DPPH radicals. All the complexes had strong binding affinities according to the molecular docking investigation: L (−11.31 kcal/mol), ZnL (−11.38 kcal/mol), and ZnL2 (−13.51 kcal/mol) against the active sites of S. aureus and (−7.92, −8.07, and −8.92) kcal/mol, respectively, against the active sites of E. coli. The Zn(II) complexes had the highest potency of biological activity.

Unveiling the 4-aminoquinoline derivatives as potent agents against pancreatic ductal adenocarcinoma (PDAC) cell lines

Common antimalarials such as artemisinins, chloroquine and their derivatives also possess potent anti-inflamantory, antiviral and anticancer properties. In the search for new therapeutics to combat difficult-to-treat pancreatic carcinomas, we unveiled that 4-aminoquinoline derivatives, with significant antiplasmodial properties and a great safety profile in vivo, have remarkable anticancer activity against pancreatic ductal adenocarcinoma (PDAC) and considerable efficacy in the xenograft model in vivo. The aim of the present study was to further investigate anticancer properties of these compounds in a drug-repurposing manner. The compounds showed profound cytotoxic effects at nanomolar to low micromolar concentration in 2D cultured cells (in vitro) and in the zebrafish PDAC xenograft model (in vivo). A deeper insight into their mechanisms of cytotoxic action showed these compounds induce apoptosis while increasing reactive oxygen species levels along with autophagy inhibition. Additional investigation of the autophagy modulation proved that tested quinoline derivatives cause P62 and LC3-II accumulation in PDAC cells alongside lysosomal alkalinization. Further, in vivo toxicity studies in the zebrafish model showed low toxicity without developmental side effects of the investigated 4-aminoquinolines, while the applied compounds effectively inhibited tumor growth and prevented the metastasis of xenografted pancreatic cells. Taken together, these results highlight the 4-aminoquinolines as privileged structures that ought to be investigated further for potential application in pancreatic carcinoma treatment.

Novel quinolin-4-ylcarbonylhydrazine having N-(3-arylacryloyl) moiety: Design, synthesis and biological evaluation as potential cytotoxic agents against MDA-MB-231 via tubulin assembly inhibition

A new set of quinolin-4-ylcarbonylhydrazine derivatives 7a-i and 9a,b bearing 3-arylacryloyl moiety has been synthesized and investigated for their potential anticancer activity. The synthetic protocol involves the following step: the target quinoline derivatives 7a-i and 9a,b appended to the acryloyl moiety were synthesized from quinolin-4-carbohydrazide intermediate with respective ethyl 2-arylamido-3-arylacrylate compounds. The cytotoxic activity study was evaluated using the functional MTT method. The most of target compounds displayed potent cytotoxic activity against MDA-MB-231 cell line. Among them, compounds 7d and 7 h were found to be promising antiproliferative agents with IC50 values of 4.04 and 1.78 μM, respectively, relative to the effective anticancer drug, Dox (IC50 = 5.33 μM). Compound 7 h exhibited cytotoxic activity by causing cell cycle to block at G2/M phase in addition to pro-apoptotic effect, as shown by flow cytometric measurement. In addition, the inhibitory action against β-tubulin polymerization was investigated. Finally, compound 7 h diminished the level of mitochondrial potential by almost 2.8-fold compared to control, indicating that the cellular death proceeds through the provoke of the intrinsic mitochondrial pathway of apoptosis.

Recent Routes in Synthesis and Biological Activity of Pyrimido[4,5-b] Quinoline Derivatives: A Review (Part II)

The synthesis of organic molecules has been a tremendous and rapid advance in the recent decade to obtain high biological and pharmacological activities. In this review, the organic synthesis of pyrimido[4,5-b]quinoline derivatives is considered an alternative method to traditional procedures for treating many diseases that affect humans. Also, by transferring electrons, stereoselective syntheses occur via organic reactions in various unnatural and natural conditions at room temperature and normal pressure. We found that the structure of pyrimido[4,5-b]quinoline derivatives was formed by substrates, bases, electrophiles, and low-level and highly stable reagents that can be broadly applied to synthesize more heterocycles. These reagents include: 2- nitrobenzaldehyde; 3-(benzyloxy)-4-methoxy-2-nitrobenzaldehyde; 4,5-dimethoxy-2- nitrobenzaldehyde; 2-aminobenzaldehyde; 2-aminoquinoline-3-carboxamide; 2-chloroquinoline3-carbaldehyde; 2-bromobenzaldehyde; 2-chloroquinoline-3-carbonitrile; 2-chloroquinoline-3- carboxylic acid; aniline; phenyl-methanamine; amino-quinoline-3-carboxylic acid /aminoquinoline-carbonitrile; amino-6,7-dimethoxy-quinoline-3-carbonitrile; amino-oxolo [4,5- g]quinolin-carboxamide; 3-(aminomethyl) quinolin-2-amine; 4-aminobenzo[d][1,3] dioxole-5- carbaldehyde; thiourea; ethyl 3-oxo-butanoate; 2-cyano-acetamide; 2-(bis (methylthio) methylene) malononitrile; ethyl 3,3-diamino-2-cyanoacrylate; naphthalene-1,4-dione; and N-carbamoyl-2- cyanoacetamide derivatives. The prepared pyrimido[4,5-b]quinoline derivatives were described through means of the following chemical reactivity: alkylation, bromination, chlorination, cyclocondensation, cyclization, acylation, oxidation-reduction, dehydration, addition reaction and Vilsmeier-Haack reaction (Vilsmeier reagent).