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Quinoline is one of the most common nitrogen-containing heterocycles owing to its fascinating pharmacological properties and synthetic value in organic and pharmaceutical chemistry. Functionalization of this moiety at different positions has allowed for varying pharmacological activities of its derivative. Several publications over the last few dec...
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In this era of sporadic advancement in science and technology, a substantial amount of intervention is being set in motion to reduce health-related diseases. Discoveries from researchers have pinpointed the usefulness of heterocyclic compounds, amongst which benzothiazepine (BTZ) derivatives have been synthesized for their various pharmacological a...
Citations
... The adherence of molecules to this rule highlights their potential suitability for oral administration, as it indicates predicted favorable absorption and distribution characteristics. The presence of a moderate number of rotatable bonds (6)(7)(8) in these molecules suggests a level of molecular flexibility that can potentially improve binding interactions with biological targets while still maintaining structural integrity and avoiding undesirable metabolic instability. ...
This study delves into the biological activity of ester compounds obtained from analogues of 6-substituted-2-chloroquinoline-3-carbaldehyde hydrazide, aiming to exploit the combined antitubercular properties of quinoline and hydrazide to create innovative hybrid compounds. The molecules underwent a meticulous multi-step synthesis process, followed by purification through recrystallization. Methodologies such as 1H NMR, 13C NMR, FTIR and Mass Spectrometry was used to confirm the molecular structures of developed derivatives. SWISSADME, an online tool, was utilized to predict the ADME properties, shedding light on their pharmacokinetic profiles. Evaluation of in vitro antitubercular activity employing the Alamar blue method highlighted compounds 4a and 4f, exhibiting noteworthy efficacy achieving threshold concentrations of 6.25 µg/ml for M. tuberculosis inhibition. These findings suggest the possibility of novel quinoline Scaffold as potential molecule for TB treatment, contributing to ongoing endeavors in TB drug discovery and potentially laying the groundwork to develop effective antitubercular therapies.
... Functionalized heterocyclic compounds are omnipresent structural skeletons in bioactive compounds [82]. Remarkably, the alkylation of indoles and quinolines received significant interest since they are common compounds in pharmaceutical and agrochemical industries [83][84][85]. Various manganese catalysts have been reported (Figure 4) for the C-alkylation of heterocyclic compounds with several alcohols, including indoles and quinolines. ...
Transition-metal-mediated “borrowing hydrogen" also known as hydrogen auto-transfer reactions allow the sustainable construction of C–C and C–N bonds using alcohols as hydrogen donors. In recent years, manganese complexes have been explored as efficient catalysts in these reactions. This review highlights the significant progress made in manganese-catalyzed C–C and C–N bond-formation reactions via hydrogen auto-transfer, emphasizing the importance of this methodology and manganese catalysts in sustainable synthesis strategies.
... Molecular hybridization is a drug design and development approach that includes merging the pharmacophore moieties of distinct bioactive compounds to discover a new compound with higher affinity and activity than the parent drugs [46]. The incorporation of imidazole, which possesses a privileged structure and a multitude of biological activities, into a single molecule via molecular hybridization along with other significant bioactive pharmacophores such as thiazole [47,48], triazole [49], indole [50,51], pyrrole [52,53], pyrrolidine [54], pyridine [55], quinoline [56,57], pyrazole [58], chalcone [59], and coumarin [60] holds great potential for addressing the aforementioned health issues. ...
In this review, we evaluated the biological activities of hybrid molecules incorporating imidazoles—a cornerstone in medicinal chemistry known for their broad pharmacological spectrum, attributed to the chemical characteristics of their nitrogen atoms. In contrast to earlier reviews, which have concentrated their attention only on a single biological activity that is connected with these hybrid molecules, this review brings together the findings of a variety of investigations that cover a wide range of significant activities including antibacterial, antifungal, antituberculosis, antiviral, anticancer, antioxidant, antidiabetic, anti-inflammatory, and analgesic effects, along with the inhibition of cholinesterase, carbonic anhydrase, and monoamine oxidase (MAO) enzymes. Furthermore, we examined significant pharmacophores such as triazole, thiazole, indole, pyrazole, quinoline, sulfonamide, pyridine, chalcone, coumarin, pyrrole, and pyrrolidine, integrated into imidazole hybrids. Molecular docking studies and structure-activity relationship (SAR) discussions provide insight into the interactions of imidazole hybrids with key enzymes and receptors. This work aspires to contribute valuable insights into the development of novel imidazole hybrids, aiming to address critical health challenges of our era.
... 12 Quinoline scaffold (1-aza-naphthalene or benzo[b]pyridine) as an important class of N-biologically active heterocycles, represent a leading and promising heterocyclic pharmacophore. 13 The quinoline scaffold is a well-recognized for diverse pharmacological applications, various natural products and bioactive drug compounds incorporate quinoline framework. 14,15 Notable medicinal applications associated with the quinoline heterocycle includes anticancer, antiviral, antitubercular and many other biological properties with signicant interest in the creation of benecial quinoline-based anticancer compounds such as Campothecin, Topotecan and Irinotecan. ...
The present work aims at design and synthesis of a congeneric series of small hybrids 5 and 6a–i featuring the privileged quinoline scaffold tethered with 2-(arylamido)cinnamide moiety as potential anticancer tubulin polymerization inhibitors. Most of the synthesized hybrids 5 and 6a–i significantly inhibited the growth of the HepG2 cell line, with IC50 ranged from 2.46 to 41.31 μM. In particular, 2-(3,4,5-trimethoxybenzamido)-4-methoxycinnamide-quinoline hybrid 6e displayed potent IC50 value toward the examined cell line, and hence chosen for further mechanistic investigations. It is noteworthy that the antiproliferative action of compound 6e highly correlated well with its ability to inhibit tubulin polymerization. In addition, the most potent hybrid 6e demonstrated a significant modification in the cellular cycle distribution, in addition to provoke of apoptotic death within the tested HepG2 cell line. Furthermore, the mechanistic approach was confirmed by a substantial upregulation in the quantity of active caspase 9 by 5.81-fold relative to untreated control cells.
... Quinazolin-4(3H)-one (1) and quinoline (2) are two important core scaffolds of heterocyclic chemistry that have been widely employed in drug design because of their broad spectrum of biological properties, such as anticancer [1][2][3][4], anti-inflammatory [5,6], and antimalarial [7,8], and antimicrobial [9][10][11] activities. In pharmaceutical chemistry, quinazolin-4(3H)-one is a structural part of the cancer drug raltitrexed (3) [12], and also serves as an important precursor to quinazoline, a required structure found in certain target drugs, for example, erlotinib and gefitinib that have been used in the treatment of non-small cell lung cancer. ...
... For the quinoline heterocycle, this skeleton demonstrates a prominent activity against malaria parasites [13]. Several quinoline derivatives, including quinine (4), chloroquine (5), and hydroxychloroquine (6) (Fig. 1) have been approved to be effective drugs for the treatment of malaria and are widely used worldwide. ...
... All chemicals were purchased from Sigma Aldrich and used without further purification. Zerumbone 14 was isolated from the roots of Zingiber zerumbet according to known procedures as described by Cuong and colleagues [21] and converted to the intermediate 15 using a protocol of Kitayama and colleagues [22]. 1 H NMR and 13 C NMR spectra were recorded at ambient temperature on a Bruker Avance 600 MHz spectrometer (Bruker Biospin, Germany) in DMSO-d 6 . Chemical shifts δ are quoted in parts per million (ppm) referenced to the residual solvent peak, (DMSO at 2.50, 3.32 ppm, and 39.5 ppm) relative to tetramethylsilane (TMS). ...
... Quinoline a benzfused nitrogen heterocycle is found in many drug molecules and plays an important role in drug development and has always remained as lead in the field of pharmaceutical prospective [5]. Quinoline derivatives have a wide range of pharmacological applications such as anticancer, antibacterial, antifungal, anthelmintic, anticonvulsant, anti-hypertensive, anti-HIV, anti-malarial, antioxidant, and anti-inflammatory activities [6][7][8][9]. Also, quinoline motiffs are present in many natural products viz., in plants particularly as alkaloids [10]. ...
... These global reactivity descriptors related to the (HOMO-LUMO) energy values may be calculated using the following Eqs. (3)(4)(5)(6)(7)(8). Content courtesy of Springer Nature, terms of use apply. ...
The present work focuses on the synthesis of novel heterocycles 2-(aryloxy)-3-(4,5-diaryl-1H-imidazol-2-yl)quinolines (6k-v) by an effective condensation reaction. These molecules exhibited fluorescent properties and hence for the proper understanding of their optical behavior and quantum yields, solvatochromic studies have been carried out. Further, frontier molecular orbitals, molecular electrostatic potential (MEP), and geometrical structure optimization have been investigated using the B3LYP/6-311G ++ (d, p) method. The energy gap between the HOMO, LUMO of the optical and energy band gap is determined by DFT and UV–visible spectra for TD-DFT studies are done. The screening of these compounds for in vitro COX-1 and COX-2 inhibition and DPPH free radical scavenging ability assays produced promising results. The binding interactions of these molecules against the COX-2 enzyme (PDB: 5IKR) were validated by docking studies.
Graphical Abstract
... The quinoline nucleus is ubiquitous in nature and plays a significant role in the development of novel heterocyclic compounds that have important pharmacological features, such as antitumoral activities [1,2]. Over time, studies of the biological activity of quinoline derivatives on diverse cancer cell lines have revealed a wide range of action mechanisms, paving the way for the development of more effective quinoline-derived drugs [3,4]. ...
To optimize the experimental conditions used for the Friedländer-type condensation, an angular fused 4-substituted quinoline steroid has been obtained in very high yield and regioselectivity using readily available 4-cholesten-3-one and 2′-aminoacetophenone. Moreover, by varying the reaction conditions and the catalyst, the corresponding linear regioisomer was also achieved with an acceptable isolated yield and high chemoselectivity. Both structures have been definitively elucidated via 2D-NMR and fully characterized.
... Benzimidazole and quinoline, are individually known for their potent pharmacological activities in various conditions like tuberculosis, 4,5 cancer, 6,7 malaria, 8,9 microbial, 10,11 fungal and bacterial infection, 12,13 viral infection, 14,15 inflammation, 16 convulsions, diabetes, hypertension, [17][18][19] and different multi-targeting hybrids inhibitors. 20,21 Moreover, Different attempts were made to design and synthesize both pharmacophores in a single structure for exhibit a synergistic effect against the targeting conditions. ...
Both, benzimidazole and quinoline pharmacophores have shown various activities against cancer, tuberculosis, malaria, fungal, viral and bacterial infections. These moieties are considered highly potent nuclei in medicinal chemistry. Thus, this research work aims to produce a synergistic effect involving both nuclei in a single structure. A Series of literature work resulted in the synthesis of novel derivatives of 2‐(1H‐1,3‐benzothiazole‐2‐yl)‐N'‐substituted quinoline‐4‐carbohydrazide 5a-q using a multiple-step reaction. Characterization of all compounds were successfully done using IR and 1HNMR, 13CNMR as well as elemental analysis. Furthermore, screening of all synthesized compounds have been shown a positive response as an anticonvulsant and antidepressant activity in mice. Compounds 5b, 5h
, 5l, and 5n have shown potentially active on pentylenetetrazole-induced seizures in mice. The synthesized compounds were also screened on a panel of 60 cell lines by the National Cancer Institute according to standard screening protocol. Ten compounds were selected and evaluated via a single high dose (10−5 M). In a onedose assay, compounds 5j and 5o showed the highest activity on leukemia (CCRF-CEM) and renal cancer (A498) with growth inhibition (GI) of 70.91 and 61.15 percent.
Aims
This study aimed to develop an editable structural scaffold for improving drug development, including pharmacokinetics and pharmacodynamics of antibiotics by using synthetic compounds derived from a (hetero)aryl-quinoline hybrid scaffold.
Methods and results
In this study, 18 CF3-substituted (hetero)aryl-quinoline hybrid molecules were examined for their potential antibacterial activity against Staphylococcus aureus by determining minimal inhibitory concentrations. These 18 synthetic compounds represent modifications to key regions of the quinoline N-oxide scaffold, enabling us to conduct a structure-activity relationship analysis for antibacterial potency. Among the compounds, 3 m exhibited potency against with both methicillin resistant S. aureus strains, as well as other Gram-positive bacteria, including Enterococcus faecalis and Bacillus subtilis. We demonstrated that 3 m disrupted the bacterial proton motive force (PMF) through monitoring the PMF and conducting the molecular dynamics simulations. Furthermore, we show that this mechanism of action, disrupting PMF, is challenging for S. aureus to overcome. We also validated this PMF inhibition mechanism of 3 m in an Acinetobacter baumannii strain with weaken lipopolysaccharides. Additionally, in Gram-negative bacteria, we demonstrated that 3 m exhibited a synergistic effect with colistin that disrupts the outer membrane of Gram-negative bacteria.
Conclusions
Our approach to developing editable synthetic novel antibacterials underscores the utility of CF3-substituted (hetero)aryl-quinoline scaffold for designing compounds targeting the bacterial proton motive force, and for further drug development, including pharmacokinetics and pharmacodynamics.
A series of new coumarin-N-heterocyclic hybrids, coumarin-quinolines 7a–e, coumarin-acridines 10b,c and coumarin-neocryptolepines 13b,c were synthesized and evaluated for their anticancer and antimicrobial activities. The structures of all synthesized hybrids were confirmed by FT-IR, ¹H-NMR, ¹³C-NMR, and MS spectrometry. The anti-proliferative activity of hybrids 7a–e, 10c and 13c were bio-evaluated using MTT-assay against colon (CaCo-2), lung (A549), breast (MDA-MB-231), and hepatocellular carcinoma (HepG-2) human cancer cell lines using doxorubicin as a reference drug. The results demonstrated that, all hybrids displayed moderate to good anti-proliferative activity against the cell lines. The most active hybrids were 7a–d and 10c against CaCo-2 cancer cell line with IC50: 57.1, 52.78, 57.29, 51.95 and 56.74 µM, and selectivity index 1.38, 1.76, 2.6, 1.96 and 0.77; respectively. While, 7a,d were potent against A549 cancer cell line with IC50: 51.72, 54.8 µM and selectivity index 1.5, 0.67; respectively. Moreover, 7c showed the most potency against MDA-MB-231 cancer cell line with IC50: 50.96 µM and selectivity index 2.20. Interestingly, docking results revealed that binding energy of the current compounds showed marked affinity values ranging from -6.54 to -5.56 kcal with interactions with the reported key amino acid SER 79. Furthermore, the antimicrobial activity of the synthesized hybrids 7a–e, 10b,c, 13b and 13c were evaluated against Gram‐positive and Gram‐negative bacterial and fungal strains. The hybrids 10b, 13b, 10c, and 13c exhibited broad-spectrum antibacterial activity against E.coli, S. mutans, and S. aureus with MIC from 3.2 to 66 µM, this hybrids also displayed antifungal activity against C. albicans with MIC values ranging from 0.0011 to 29.5 µM. In-silico investigation of the pharmacokinetic properties indicated that tested hybrids had high GI absorption, low Blood Brain Barrier (BBB) permeability in addition to cell membrane penetrability.
