Quinoline Heterocycles Research Articles

Zirconium-catalyzed one-pot synthesis of benzoxazoles using reaction of catechols, aldehydes and ammonium acetate

In this study, an efficient method for the synthesis of benzoxazoles by coupling catechols, aldehydes and ammonium acetate using ZrCl4 as catalyst in ethanol is reported. A wide range of benzoxazoles (59 examples) are smoothly produced in high yields (up to 97%). Other advantages of the method include large-scale synthesis and the use of oxygen as an oxidant. The mild reaction conditions allowed late-stage functionalization, facilitating access to several derivatives with biologically relevant structures such as β-lactam and quinoline heterocycles.

Cu‐catalyzed dehydrogenative CO arylation for the synthesis of 6‐methyl benzofuro[3,2‐c] quinoline derivatives

AbstractA novel strategy for the synthesis of 6‐methyl benzofuro[3,2‐c] quinoline derivatives via copper‐catalyzed dehydrogenative CO arylation has been presented. Optimization studies have been carried out by varying various catalysts, bases, solvents, and other physical parameters. Keeping use of this dehydrogenative cross‐coupling CO arylation reaction, a variety of bioactive building blocks like fused benzofuro quinoline heterocycles were smoothly assembled in moderate to higher yields.

Clinical Use of COX-2 Inhibitors Containing Quinoline Heterocycle as a Selective Therapeutic Agents for Complementary Medicine

Clinical Use of COX-2 Inhibitors Containing Quinoline Heterocycle as a Selective Therapeutic Agents for Complementary Medicine

Highly Selective Cyclization and Isomerization of Propargylamines to Access Functionalized Quinolines and 1-Azadienes.

Developing new organic reactions with excellent atom economy and high selectivity is significant and urgent. Herein, by ingeniously regulating the reaction conditions, highly selective transformations of propargylamines have been successfully implemented. The palladium-catalyzed cyclization of propargylamines generates a series of functionalized quinoline heterocycles, while the base-promoted isomerization of propargylamines affords diverse 1-azadienes. Both reactions have good functional group tolerance, mild conditions, excellent atom economy and high yields of up to 93%. More importantly, these quinoline heterocycles and 1-azadienes could be flexibly transformed into valuable compounds, illustrating the validity and practicability of the propargylamine-based highly selective reactions.

Cytotoxic activity of 7-R-4-substituted quinoline

Annotation. Quinoline derivatives are important compounds for chemical synthesis and the development of new drugs and pesticides. The practical application of a number of substances with a quinoline heterocycle in medical practice and agriculture is well known. Quinoline compounds exhibit a wide range of biological effects, including cytotoxic activity. Phytotoxic (cytotoxic) activity of 15 4-substituted quinoline derivatives were studied and compared with reference drugs. 7-R-4-substituted quinoline derivatives were tested by root test on Cucumis sativus L. seedlings at different concentrations. Distilled water was used as reference in the control experiment. During the experiment, all factors were taken into account to create equal conditions for all studied elements. The obtained results were processed using the program “STATISTICA® for Windows 6.0” (StatSoft Inc, No. АХХР712D833214FAN5) by methods of variational statistics using the Student’s t-test. 7-R-4-substituted quinoline derivatives turned out to be predominantly cytotoxic compounds, that corresponds to the “structure-action” dependence between the structure of investigated compounds and their biological activity. All tested compounds have a pronounced phytotoxic effect at the concentration of 500 μg/ml. The most pronounced cytotoxic effect was recorded among the (heteryl)cysteamine derivatives – β-(quinolin-4-yl)cysteamine dihydrochloride, β-(7-chloroquinolin-4-yl)cysteamine dihydrochloride, 3-((7-chloroquinolin-4-yl)thio)propanoic acid hydrochloride. Derivatives of (heterylthio)acetic acids have shown growth-promoting effects at low concentrations. Thus, 2-(quinolin-4-ylthio)- and 2-(7-chloroquinolin-4-ylthio) acetic acids have shown the most active effect (50-250% compared to control group) at concentrations of 1-20 μg ml. Sodium 3-((7-chloroquinolin-4-yl)thio)propanoate has indicators that exceed the control by 7-60%, with the most effective growth of the main root of seedlings by 30% among all studied substances at the concentration of 100 μg/ml compared to control group. Some compounds have cytotoxic activity that can be used in crop production as growth regulators of agricultural plants.

The Versatile Quinoline and Its Derivatives as anti-Cancer Agents: An Overview

Quinoline heterocycles have been considered important structures due to their diverse applications in organic synthesis, coordination chemistry, as well as in the fields of drug design and development. Consequently, many researchers around the globe have focused on the production of these molecules as objective lead compounds and exploit their biological activities. Herein, the presented review provides an overview of anticancer agents and natural sources of quinolines and includes a summary of marketed drugs. Advanced synthetic analogs of quinoline derivatives and their anticancer activity have been provided.

Recent Advances on Synthesis of Fused Chromeno‐Quinoline Heterocycles under Transition Metal‐Free Condition

AbstractAmong the various other organic compounds, the compounds having heterocyclic core are extensively circulated in nature and are often crucial for life. The concerned heterocyle may or may not be aromatic. They often show a variety of physiological, industrial and also theoretical significance. Quinoline derivatives are very popular anti‐biotics and benzopyran or chromenes is another important heterocyclic moiety found widely in naturally occurring plant products like fruits and vegetables. However, when chromene and quinoline are present in a molecule in fused form, a subclass of very important bio‐active chromene‐fused quinoline heterocycles is formed. This review covers recent reports on transition metal‐free synthesis of chromeno‐quinoline derivatives in short and hassle‐free reaction protocols.

Quinoline heterocyclic containing plant and marine candidates against drug-resistant Mycobacterium tuberculosis: A systematic drug-ability investigation

Today, tuberculosis (TB) caused by the acid-fast bacilli, Mycobacterium tuberculosis (Mtb) is the most infectious killer disease globally with high morbidity and mortality rates. The rapid development of multi-drug-resistant (MDR) strains via intrinsic (efflux pumps) and acquired (biological mutations) mechanisms reduce the efficacy of applied anti-TB regimens. Nevertheless, only bedaquiline (BDQ) and pretomanid (PMD) were added to anti-TB therapy in the last decade. The existing anti-TB drugs also exhibited cytotoxicity and hepatotoxicity from long-term treatment. Thus, exploring or developing potential and less toxic anti-TB candidates, preferably natural-based candidates, is the call of the day. At present, ‘quinoline’ could be considered one of the versatile scaffolds presented in most mainstream medicines from comprehensive drug reports. Notably, BDQ with two clinically evaluating anti-TB candidates, TBJA-587 and DC-159a was motivated for utilizing quinoline heterocycles. Accordingly, we have selected 65 natural quinoline heterocycles bearing potential anti-TB agents (40 plant-derived and 25 marine-derived) within MIC value ≤ 50 μg/mL from an extensive literature search. Briefly, source, drug chemistry, structural activity relationship, prior pharmacokinetics profiles with drug-ability, toxicity, and hierarchical clustering analysis using various computational tools to identify the most ‘drug-able lead’ candidate is the uniqueness of the review. From extensive drug analysis, tetrandrine, 2′-nortiliacorinine, tiliacorine, globospiramine, evocarpine, allocuspareine from plant sources, and ecteinascidin 770, 6-hydroxymanzamine E, (−)-8-hydroxymanzamine A, ecteinascidin 786, manzamine F from marine sources are the most potential-cum-drug-able anti-TB candidates. We hope the systematic and critical drug analyses on quinoline-bearing natural anti-TB candidates are helpful to design potential-cum-less toxic anti-TB drugs in the future.

Novel (quinolin-8-yl-oxy)-pyrazole/thiophene derivatives: Synthesis, characterization and their pharmacological evaluation

Two novel series of pyrazole and thiophene-linked quinoline analogues via amide bond were conveniently synthesized and characterized by IR, NMR, and HRMS analysis. The synthesized compounds were evaluated for their antimicrobial, anti-inflammatory, and anti-leukemic activity. The antimicrobial evaluation of the target compounds clearly showed that compound 11c has better activity compared to other compounds against tested pathogens. The anti-inflammatory assay of the selected compounds showed that 12c with IC50 value 118.73 µg/ml exhibited significant activity than standard drug Aspirin (IC50, 107.75 µg/ml). The compound 12a out of the twelve newly prepared quinoline heterocycles displayed superior antileukemic activity and was comparable with the standard drug against human monocytic leukemia cell lines (THP-1). Representing the two different quinolinyl-pyrazole/thiophene analogues, compounds 11d, 11e, and 12a displayed the remarkable cytotoxicity against THP-1 cell lines with IC50 values 112.46, 105.42, and 98.88 µg/ml respectively.

Synthesis and Evaluation of the Antibacterial and Antioxidant Activities of Some Novel Chloroquinoline Analogs

Quinoline heterocycle is a useful scaffold to develop bioactive molecules used as anticancer, antimalaria, and antimicrobials. Inspired by their numerous biological activities, an attempt was made to synthesize a series of novel 7-chloroquinoline derivatives, including 2,7-dichloroquinoline-3-carbonitrile (5), 2,7-dichloroquinoline-3-carboxamide (6), 7-chloro-2-methoxyquinoline-3-carbaldehyde (7), 7-chloro-2-ethoxyquinoline-3-carbaldehyde (8), and 2-chloroquinoline-3-carbonitrile (12) by the application of Vilsmeier–Haack reaction and aromatic nucleophilic substitution of 2,7-dichloroquinoline-3-carbaldehyde. The carbaldehyde functional group was transformed into nitriles using POCl3 and NaN3, which was subsequently converted to amide using CH3CO2H and H2SO4. The compounds synthesized were screened for their antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Streptococcus pyogenes. Compounds 6 and 8 showed good activity against E. coli with an inhibition zone of 11.00 ± 0.04 and 12.00 ± 0.00 mm, respectively. Compound 5 had good activity against S. aureus and P. aeruginosa with an inhibition zone of 11.00 ± 0.03 mm relative to standard amoxicillin (18 ± 0.00 mm). Compound 7 displayed good activity against S. pyogenes with an inhibition zone of 11.00 ± 0.02 mm. The radical scavenging activity of these compounds was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), and compounds 5 and 6 displayed the strongest antioxidant activity with IC50 of 2.17 and 0.31 µg/mL relative to ascorbic acid (2.41 µg/mL), respectively. The molecular docking study of the synthesized compounds was conducted to investigate their binding pattern with topoisomerase IIβ and E. coli DNA gyrase B. Compounds 6 (−6.4 kcal/mol) and 8 (−6.6 kcal/mol) exhibited better binding affinity in their in silico molecular docking against E. coli DNA gyrase. The synthesized compounds were also found to have minimum binding energy ranging from −6.9 to −7.3 kcal/mol against topoisomerase IIβ. The SwissADME predicted results showed that the synthesized compounds 5–8 and 12 satisfy Lipinski’s rule of five with zero violations. The ProTox-II predicted organ toxicity results revealed that all the synthesized compounds were inactive in hepatotoxicity, immunotoxicity, mutagenicity, and cytotoxicity. The findings of the in vitro antibacterial and molecular docking analysis suggested that compound 8 might be considered a hit compound for further analysis as antibacterial and anticancer drug. The radical scavenging activity displayed by compounds 5 and 6 suggests these compounds as a radical scavenger.

Heterocyclic Diamines with Leishmanicidal Activity.

Leishmaniasis is one of the world's most neglected diseases with a worldwide prevalence of 12 million people. There are no effective human vaccines for its prevention, and outdated drugs hamper treatment. Therefore, research aimed at developing new therapeutic tools to fight leishmaniasis remains a crucial goal today. With this purpose in mind, here, we present 10 new compounds made up by linking alkylated ethylenediamine units to pyridine or quinoline heterocycles with promising in vitro and in vivo efficacy against promastigote and amastigote forms of Leishmania infantum, Leishmania donovani, and Leishmania braziliensis species. Three compounds (2, 4, and 5) showed a selectivity index much higher in the amastigote form than the reference drug glucantime. These three derivatives affected the parasite infectivity rates; the result was lower parasite infectivity rates than glucantime tested at an IC25 dose. In addition, these derivatives were substantially more active against the three Leishmania species tested than glucantime. The mechanism of action of these compounds has been studied, showing alterations in glucose catabolism and leading to greater levels of iron superoxide dismutase inhibition. These molecules could be potential candidates for leishmaniasis chemotherapy due to their effectiveness and their ready synthesis.

Updates on the versatile quinoline heterocycles as anticancer agents

Abstract Quinoline motifs have befallen significant molecules due to their assortment of interest in medicine, chemical synthesis, coordination chemistry, also in the field of applied chemistry. Therefore, various researchers have produced these molecules as objective structures and studied their natal potential. The current chapter endows with concise attention about cancer, anticancer agents, sources (natural) of quinoline, and together with an innovative scope of quinoline-related medicines. Further, the present section gives knowledge concerned with the anticancer activity of synthesized quinolines and their derivatives.

Regiochemical Effects on the Carbohydrate Binding and Selectivity of Flexible Synthetic Carbohydrate Receptors with Indole and Quinoline Heterocyclic Groups.

Synthetic carbohydrate receptors (SCRs) that bind cell-surface carbohydrates could be used for disease detection, drug-delivery, and therapeutics, or for the site-selective modification of complex carbohydrates but their potential has not been realized because of remaining challenges associated with binding affinity and substrate selectivity. We have reported recently a series of flexible SCRs based upon a biaryl core with four pendant heterocyclic groups that bind glycans selectively through noncovalent interactions. Here we continue to explore the role of heterocycles on substrate selectivity by expanding our library to include a series of indole and quinoline heterocycles that vary in their regiochemistry of attachment to the biaryl core. The binding of these SCRs to a series of biologically-relevant carbohydrates was studied by 1H NMR titrations in CD2Cl2 and density-functional theory calculations. We find SCR030, SCR034 and SCR037 are selective, SCR031, SCR032, and SCR039 are strong binders, and SCR033, SCR035, SCR036, and SCR038 are promiscuous and bind weakly. Computational analysis reveals the importance of C-H⋯π and H-bonding interactions in defining the binding properties of these new receptors. By combining these data with those obtained from our previous studies on this class of flexible SCRs, we develop a series of design rules that account for the binding of all SCRs of this class and anticipate the binding of future, not-yet imagined tetrapodal SCRs.

ПРОГНОЗОВАНИЙСКРИНІНГБІОЛОГІЧНОЇАКТИВНОСТІS-АЛКІЛОВИХЕСТЕРІВ 8-ХІНОЛІНТІОСУЛЬФОКИСЛОТИ

Quinoline and its derivatives are important compounds for the chemical synthesis and development of novel drugs. Practical application of a number of substances with quinoline heterocycle is already known in medical practice.

Rhodium(III)-Catalyzed Oxidative Annulation of 4-Aminoquinolines and Acrylate through Two Consecutive C(sp2)-H Activations.

The C-H annulation of the five-position of quinolines and acrylates to afford heterocycles is an active field of research in organic synthesis. Herein the annulation of 4-aminoquinolines with acrylates through two consecutive C-H activations catalyzed by Rh(III) is described. The reaction proceeds with high atom efficiency under mild reaction conditions, and this protocol will provide appealing strategies for the synthesis of fused quinoline heterocycles.

Photophysicochemical Properties and In Vitro Phototherapeutic Effects of Iodoquinoline- and Benzothiazole-Derived Unsymmetrical Squaraine Cyanine Dyes

The search to replace conventional cancer treatment therapies, such as chemotherapy, radiotherapy and surgery has led over the last ten years, to a substantial effort in the development of several classes of photodynamic therapy photosensitizers with desired photophysicochemical and photobiological properties. Herein we report the synthesis of 6-iodoquinoline- and benzothiazole-based unsymmetrical squaraine cyanine dyes functionalized with amine groups located in the four-membered central ring. Their photodegradation and singlet oxygen production ability, as well as their in vitro photocytotoxicity against Caco-2 and HepG2 cell lines using a 630.8 ± 0.8 nm centered light-emitting diode system, were also investigated. All photosensitizer candidates displayed strong absorption within the tissue transparency spectral region (650–850 nm). The synthesized dyes were found to have moderate light stability. The potential of these compounds is evidenced by their cytotoxic activity against both tumor cell lines, highlighting the zwitterionic unsubstituted dye, which showed more intense photodynamic activity. Although the singlet oxygen quantum yields of these iodinated derivatives are considered low, it could be concluded that their introduction into the quinoline heterocycle was highly advantageous as it played a role in increasing selective cytotoxicity in the presence of light. Thus, the novel synthesized dyes present photophysicochemical and in vitro photobiological properties that make them excellent photosensitizer candidates for photodynamic therapy.

Iron(II) coordination complexes with panchromatic absorption and nanosecond charge-transfer excited state lifetimes.

Replacing current benchmark rare-element photosensitizers with ones based on abundant and low-cost metals such as iron would help facilitate the large-scale implementation of solar energy conversion. To do so, the ability to extend the lifetimes of photogenerated excited states of iron complexes is critical. Here, we present a sensitizer design in which iron(II) centres are supported by frameworks containing benzannulated phenanthridine and quinoline heterocycles paired with amido donors. These complexes exhibit panchromatic absorption and nanosecond charge-transfer excited state lifetimes, enabled by the combination of vacant, energetically accessible heterocycle-based acceptor orbitals and occupied molecular orbitals destabilized by strong mixing between amido nitrogen atoms and iron. This finding shows how ligand design can extend metal-to-ligand charge-transfer-type excited state lifetimes of iron(II) complexes into the nanosecond regime and expand the range of potential applications for iron-based photosensitizers.

Isocyano(triphenylphosphoranylidene)acetates: Key to the One-Pot Synthesis of Oxazolo[4,5-c]quinoline Derivatives via a Sequential Ugi/Wittig/aza-Wittig Cyclization Process.

A one-pot novel strategy is described for the construction of various oxazolo[4,5-c]quinoline derivatives starting from the isocyano(triphenylphosphoranylidene)acetates, aldehydes, amines, and 2-azidobenzoic acids. The reactions generated the target products directly in moderate to good yields via a sequential Ugi/Wittig/aza-Wittig cyclization process. The salient features of the method are that all three groups of the multifunctional isocyanides were involved in the reaction with broad substituent scopes and mild reaction conditions, making the protocol a useful contribution to the synthesis of oxazolo[4,5-c]quinoline heterocycles.

Iodine mediated in situ generation of R-Se-I: application towards the construction of pyrano[4,3-b]quinoline heterocycles and fluorescence properties.

In this paper, we report the iodine mediated in situ generation of R-Se-I and further its application towards the construction of pyrano[4,3-b]quinolin-1-one derivatives. The structural elaboration of 1-chloro-8-methyl-3-phenylbenzo[b][1,6]naphthyridine 6 was successfully achieved by Sonogashira, Suzuki coupling and dehalogenation reactions. Finally, the synthesized compounds 4a, 5a, 5b, 6, and 7a-7c were studied for photophysical properties including UV-absorption, fluorescence, and quantum yield studies. The synthesized pyranoquinoline derivatives showed λmax, Fmax and Φf values in the range of 391-447 nm, 436-486 nm and 0.004-0.301, respectively in chloroform solvent.

ChemInform Abstract: Cobalt‐Catalyzed Synthesis of Quinolines from the Redox‐Neutral Annulation of Anilides and Alkynes.

AbstractThis new method shows a remarkable regioselectivity in the case of meta‐substituted anilides (IVa,b) and unsymmetric acetylenes (VIII).