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Recent advances in the synthesis of biologically and

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Cite this: RSC Adv., 2020, 10, 20784

pharmaceutically active quinoline and its
analogues: a review
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Abdanne Weyesa and Endale Mulugeta *

Recently, quinoline has become an essential heterocyclic compound due to its versatile applications in the
fields of industrial and synthetic organic chemistry. It is a vital scaffold for leads in drug discovery and plays
a major role in the field of medicinal chemistry. Nowadays there are plenty of articles reporting syntheses of
the main scaffold and its functionalization for biological and pharmaceutical activities. So far, a wide range
of synthesis protocols have been reported in the literature for the construction of this scaffold. For example,
Gould–Jacob, Friedländer, Pfitzinger, Skraup, Doebner–von Miller and Conrad–Limpach are well-known
classical synthesis protocols used up to now for the construction of the principal quinoline scaffold.
Transition metal catalysed reactions, metal-free ionic liquid mediated reactions, ultrasound irradiation
reactions and green reaction protocols are also useful for the construction and functionalization of this
Received 26th April 2020
Accepted 11th May 2020
compound. The main part of this review focuses on and highlights the above-mentioned synthesis
procedures and findings to tackle the drawbacks of the syntheses and side effects on the environment.
DOI: 10.1039/d0ra03763j
Furthermore, various selected quinolines and derivatives with potential biological and pharmaceutical
[Link]/rsc-advances activities will be presented.

applications. 1-Azanapthalene and benzo[b]pyridine are used as

1. Introduction alternative names for quinoline (Fig. 1).
Quinoline is the most ubiquitous heterocyclic aromatic It has a characteristic double-ring structure containing
compound with a potential for industrial and medicinal a benzene ring fused with a pyridine moiety, with the molecular
formula C9H7N.1 Quinoline is an essential segment of both
Department of Applied Chemistry, School of Applied Natural Science, Adama Science natural and synthetic compounds. In particular, the pyr-
and Technology University, P. O. Box: 1888, Adama, Ethiopia. E-mail: endale. anoquinoline ring system has gained considerable attention as
mulugeta@[Link]

Abdanne Weyesa was born in Endale Mulugeta received his

Wolisso, Ethiopia. She gradu- MSc from the College of Natural
ated from Adama Science and and Computational Sciences,
Technology University where she Department of Chemistry, Addis
remained to carry out her MSc Ababa University, Ethiopia in
studies under the supervision of 2010 and his PhD from the
Dr Endale Mulugeta. Her College of Natural Sciences,
research focuses on the synthesis Department of Chemistry,
of bioactive chalcone derivatives Kangwon National University,
anchored with heterocyclic South Korea in 2018. He joined
compounds in different classes Adama Science and Technology
that have pharmacological University as an Assistant
activities. Professor of Organic Chemistry
in 2018. His research topics include the study and development of
new methods and synthetic approaches towards organic
compounds, as well as a focus on developments in the synthesis of
heterocyclic organic compounds of different classes that have
pharmacological activity.

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Fig. 1 Chemical structure of quinoline.

it is a core structure, constituting the basic skeleton of a number

of alkaloids.2 Generally quinoline is present in pharmacologi-
cally active natural products and in synthetic products. This
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compound is used mainly as a central template for the synthesis

of various drugs. Quinoline is a weak tertiary base and can form
salts with acids. It exhibits similar reactions to pyridine and
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benzene and can also participate in both electrophilic and

nucleophilic substitution reactions. It is nontoxic to humans.3
For the construction and functionalization of this noble
compound and its derivatives, an enormous number of
synthesis techniques have been reported, among which
conventional or classical methods, transition metal free cata-
lysed methods, ultrasound irradiation reactions and greener
chemical processes have been well explored. Most of the time
scholars explore classical reaction methodologies, such as Fig. 2 Structures of bioactive compounds from natural sources.
Gould–Jacobs,4 Friedländer,5 Ptzinger,6 Skraup,7 Doebner–von
Miller,8 and Conrad–Limpach,9 and modify them with eco- cyclization reaction.4 In this procedure 4-hydroxyquinoline 16 is
friendly transition metal mediated, ultrasound irradiation prepared from aniline (14) and diethyl ethox-
reactions or greener protocols.10,11 ymethylenemalonate (15) involving series of reactions to
Currently, studies revealing numerous natural products and provide quinoline 16 (Scheme 1).
synthetic derivatives incorporating a quinoline scaffold have This protocol helps in the preparation of various commer-
attracted scholars' attention because they exhibit a broad range cially available drugs based on a quinoline scaffold as the core
of biological and pharmaceutical activities. skeleton. For instance, the preparation of the well-known
For example antibacterial, antioxidant, anticancer, anti- nonsteroidal anti-inammatory drugs octafenine and glafe-
inammatory, antimalarial, antifungal and antileishmanial nine relies on this synthesis methodology.4
activities have been well studied.12 Shang and co-workers reported
a comprehensive review on alkaloids with a quinoline moiety as 2.2. Friedländer quinoline synthesis
a core scaffold, isolated from compounds from natural sources
In this procedure ortho-substitution of aniline 17 and aldehyde
and showing bioactivity potential.13 The review comprehensively
or ketone 18 with a reactive a-methylene group via condensa-
organized into two focal sections. First various synthesis strategies
tion followed by cyclodehydration reactions affords compound
will be addressed to highlight the original reaction procedures
19 (Scheme 2). In this reaction procedure, regioselectivity is
and modications in the recent literature related to all the
a challenging issue when unsymmetrical ketones are used.5 The
synthetic strategies accordingly. Then novel pharmaceutically and
reaction is well catalysed using a base or acid, such as
biologically active quinolines will be explored (Fig. 2).
a Brønsted acid or a Lewis acid, and ionic liquids can also
activate the reaction well. Furthermore, it can proceed smoothly
2. Synthesis of quinoline and its without a catalyst by heating the mixture. The merit of this
reaction procedure is the scope of substrates of various func-
derivatives tional groups that are well tolerated on both arylamine and
So far scholars have explored copious synthesis protocols to ketone moieties.
construct and functionalize the quinoline scaffold. Here, we focus
on a review of the classical synthesis procedures named Gould– 2.3. Modied Friedländer quinoline synthesis
Jacob, Friedländer, Ptzinger, Skraup, Doebner–von Miller, and Anand and co-workers operationally developed a simple, highly
Conrad–Limpach reactions, transition metal catalysed reactions, efficient, practical and convenient one-pot method for the
transition metal free ionic liquid mediated reactions, ultrasound synthesis of a broad scope of quinoline derivatives.6 Here, by
irradiation reactions, and greener chemical processes for the
synthesis of quinoline and its analogues will be discussed briey.

2.1. Gould–Jacob quinoline synthesis

Various quinoline scaffolds with substituents at carbon-4 can be
prepared through cascade reactions known as the Gould–Jacob Scheme 1 General scheme of the Gould–Jacobs quinoline synthesis.

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Scheme 2 General reaction scheme of Friedländer quinoline Scheme 5 Synthesis of quinoline derivative 28 through the Pfitzinger
synthesis. reaction.
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modications in a one-step and one-pot method to synthesize

quinoline-4-carboxylic acids 28 in water (Scheme 5). Isatin (27)
was reuxed with enaminone 26 in the presence of an aqueous
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solution of KOH or NaOH, and subsequent acidication using

dilute HCl to prepare quinoline-4-carboxylic acid (28) in good to
excellent yields.7 The authors claimed that using enaminone as
Scheme 3 General reaction scheme of modified Friedländer quinoline a replacement for 1,3-dicarbinols improves the yield and prac-
synthesis. ticality of the reaction.

using 2-bromobenzaldehyde (20), acyclic or cyclic 1,3-diketone 2.5. Skraup/Doebner–von Miller quinoline synthesis
(21) and sodium azide in a three-component reaction protocol A synthesis of quinoline via aniline and glycerine in the pres-
in the presence of an air-stable, eco-efficient and inexpensive ence of a strong acid and an oxidant under reux was revealed
catalyst, quinoline 22 is prepared in good yields. In this reaction by Skraup and co-workers.8 Here, a crotonaldehyde interme-
copper salt-D-glucose helps to generate Cu(I) species in situ diate is generated in situ from glycerol 30. Subsequently aniline
through reduction in aqueous ethanol as a green solvent, and 29 is added to the reaction under heating to provide quinoline
proline is used as a ligand and proton source to synthesize the 31. The reaction of substituted acrolein 32 with aniline 29 in the
target compound (Scheme 3). This protocol follows an Ullmann- presence of an oxidant to provide quinoline 33 is known as the
type coupling reaction where nucleophilic substitution of Br Doebner–von Miller protocol (Scheme 6).
from 2-bromobenzaldehyde (20) with sodium azide gives an The fundamental drawbacks of the Skraup and Doebner–von
azido complex intermediate. The azido–Cu complex is sub- Miller syntheses are that both turn out to be violently
jected to reductive elimination followed by dehydrative cyclo- exothermic during the progress of the reaction, and the variety
condensation, providing the desired quinoline 22. of oxidants and the highly acidic medium required make
The authors claim that this method worked nicely with both isolation of the desired product tedious. Regioselectivity is also
electron-donating and electron-withdrawing substituent groups a concern when meta or 3,4-disubstituted anilines are used.9 2-
at the ortho-, meta-, and para-positions of the phenyl ring.6 methylquinoline and its derivatives have shown substantial
biological activities. However, there are different techniques for
2.4. Ptzinger quinoline synthesis the synthesis of 2-methylquinoline, and Doebner–von Miller is
This procedure is also known as the Ptzinger–Borsche reac- the best. Yalgin and co-workers report the synthesis of 2-methyl-
tion. Here isatin 23 reacting with a-methylene carbonyl quinoline 36 using a modied Doebner–von Miller reaction
compound 24 in the presence of a base in ethanol provides protocol in the presence of a strong acid in a ow reactor with
substituted quinoline derivative 25 (Scheme 4).6 In this reaction aniline and acrolein.15 2-Methylquinoline derivative 36 synthesized
protocol, isatic acid is formed from isatin 23 and condensed using a continuous ow in water through Doebner–Miller reaction
with a-methylene carbonyl compound 24 in the presence of
a strong base. Subsequent decarboxylation affords quinoline 25.
This procedure is an extension of the Friedländer quinoline
synthesis protocol. The reaction basically depends on the more
stable isatin varieties instead of the ortho-aminoaryl moieties
that are the basic starting materials for the preparation of
quinoline via the former reaction protocol.7 Elghamry and co-
workers used a similar reaction protocol with minor

Scheme 4 General reaction scheme of the Pfitzinger quinoline Scheme 6 General reaction scheme of Skraup/Doebner–von Miller
synthesis. quinoline synthesis.

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Scheme 7 General reaction scheme of Doebner–von Miller quinoline

synthesis.

procedure. This method is a rapid and green route for the

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synthesis of quinoline derivatives to provide a good to excellent Scheme 9 Synthesis of a quinoline derivative using ultrasound
yields (Scheme 7).14 irradiation.
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2.6. Combes/Conrad–Limpach quinoline synthesis

yields.16 Quinoline 45 can be easily functionalized at the 4-
The Combes/Conrad–Limpach reaction is the condensation of chloro position with o-phenylenediamine 43, and further reac-
a primary aryl amine with a 1,3-diketone or b-keto-aldehyde or ted with unsymmetrical ketone 44 via a green chemistry
1,3-dialdehyde, giving an enamine intermediate which is protocol to provide quinoline derivative 45.
further heated in a strong acid, and later cyclodehydration to Xie and co-workers report C2-sulfonation of N-oxide quino-
afford quinoline. Here, the condensation of primary aryl amine line (46) using sulfonyl chloride 47 in the presence of Zn-dust,
37 with b-diketone 40 in acid catalysis, followed by ring closure with water as a solvent via an ultrasound-assisted protocol,
of a Schiff base, affords quinoline 41 (Scheme 8).10 providing quinoline 48 in moderate yield.17 Here, sulfonyl
Using the same reaction procedure the Conrad–Limpach chloride 47 is rst reduced using Zn-dust. The generated
scheme can be used to prepare various quinoline derivatives intermediate is coordinated with N-oxide quinoline 46. Finally,
using b-ketoester 38 in place of b-diketone 40. Both procedures the target compound 48 is synthesized through an intra-
follow the condensation of arylamine with b-ketoester or b- molecular nucleophilic addition reaction (Scheme 10).
diketone by a further cyclodehydration reaction and heating in
strong acid to prepare the target compounds.
2.8. Transition metal free quinoline synthesis

2.7. Ultrasound irradiation reactions Various scholars report the synthesis of quinoline and its
derivatives via metal-free mediated reaction protocols, such as
The reaction time, product yields and qualities of this reaction
ionic liquid, simple acid or base catalyst, using molecular
procedure are better than those from the above-mentioned
iodine and catalyst-free reactions. The above-mentioned
quinoline synthesis protocols. It is one of the greener quino-
procedures are considered to be green chemical processes.
line synthesis protocols. Using an ultrasound irradiation reac-
Conducting reactions using the above strategies can achieve
tion procedure via two sequential reactions, SN2 followed by
a high level of atom efficiency. The reaction media are recy-
a condensation reaction, quinoline 45 can be synthesized in
clable, they provide high yields, have a short reaction time, are
good yield (Scheme 9).12
practical to operate under mild reaction conditions, conduct
This procedure has the advantages of a short reaction time
the reduction in a number of steps, decrease waste and are eco-
and easy isolation of the product and provides good-to-excellent
friendly.18 Here, two amine derivatives, enamide 49 and imine
50, react in the presence of iodine in air to afford quinoline 51
(Scheme 11). In order to improve the reaction efficiency, various
types of catalysts were explored. Among all these catalysts,
iodine exhibited the highest yields. Moreover, the reaction has
attracted a great deal of attention with its benets of low
toxicity, ability to operate under mild reaction conditions, low-
cost starting materials and broad scope of substrates.
The three-component reaction of methyl ketone 52, aryl-
amine 53, and a-ketoester 54 in the presence of iodine and
a catalytic amount of hydroiodic acid provides quinoline 55. In
this reaction the HI co-product acts as a promoter with good

Scheme 8 General reaction scheme of the Combes/Conrad–Lim- Scheme 10 Synthesis of a quinoline derivative using a non-metal
pach quinoline synthesis. catalyst.

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Scheme 11 Synthesis of a quinoline derivative using a non-metal

catalyst.

Scheme 14 Synthesis of quinoline derivative 60.

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is well-known for use as a sulfonating reagent in the following

reactions, because it is stable to moisture and is safe and easy to
handle. Additionally, Han and co-workers report the synthesis
Scheme 12 Three-component iodine-catalysed quinoline synthesis.
of 2-sulfonylquinoline 69 using quinoline N-oxide with sodium
sulnate as starting materials in the presence of K2S2O8 as an
oxidant under an inert atmosphere in a mixed solvent system.25
functional compatibility (Scheme 12).19 Under transition metal Peng and co-workers amended previously reported protocols
free reaction conditions oxygen acts as an oxidant, where 2- and reported the synthesis of 2-sulfonylquinoline 69 from
(aminomethyl)-aniline 56 reacts with aromatic ketone 57 to quinoline N-oxide and sodium sulnate via an easy, metal-free,
provide the corresponding quinoline 58 with excellent yield oxidant-free and solvent-free method under mild reaction
(Scheme 13). Wu and co-workers reported that the reaction conditions using TsCl in water.26 Furthermore, 2-sulfonylqui-
procedure for the synthesis of quinoline can be achieved under noline 69 was synthesized from quinoline N-oxide and sulfonic
aerobic reaction conditions without the presence of a catalyst, acid 68 using organic dye as a catalyst (Scheme 17).27
with lithium chloride salt additive in dimethylacetamide The reaction was performed with a greener process protocol,
solvent.20 Following this reaction procedure ketones bearing and in ambient air to provide good to excellent yields.
strong electron-withdrawing or electron-donating groups could
react smoothly and in an eco-friendly way to provide the desired
product. 2.9. Transition metal mediated protocols
Carbaldehyde 59 reacted with substituted aniline 29 without Xu and co-workers reported the one-pot synthesis of substituted
a catalyst to provide quinoline 60 in excellent yield (Scheme quinoline 71 with a broad scope of substrates using a transition
14).21 The reaction is performed at room temperature, with Co(III) metal mediated reaction protocol.28 Co(III) catalysis via
a short reaction time, providing excellent yield with no catalyst a cascade of reactions, C–H activation, carbonylation and
required (Scheme 14). cyclization of aniline 29 and ketone 70 with paraformaldehyde
Through a convenient two consecutive steps ethyl-4-hydroxy- provide various useful quinoline derivatives (Scheme 18).
2-methylquinoline-3-carboxylate (63) was synthesized. Using Benets of the procedure are the broad scope of substrates with
solid triphosgene in THF, commercially available 2-amino- tolerance to various functional groups and the affordance of
benzoic acid 61 converted to isatoic anhydride 62, reacted with good to excellent yields. Moreover, it releases water and
the sodium enolate of ethyl acetoacetate in warm DMA, to afford hydrogen gas as by-products.
substituted quinoline 63 (Scheme 15).22 Das and co-workers reported the synthesis of various poly-
Zhu and co-workers reported an environmentally friendly substituted quinolines 75 from commercially available a-
reaction methodology to prepare quinoline 66.23 In this reaction
procedure the cheap and commercially available material 2-
nitrobenzyl alcohol (64) reacted with ketone 65 via an intra-
molecular redox process to afford synthetically important
quinoline 66 in moderate yields (Scheme 16).
2-Sulfonylquinoline 69 was prepared smoothly without
a base or organic solvent from quinoline N-oxide 46 and sodium
sulnate 67 using a metal-free and dual radical coupling reac-
tion protocol devised by Xie and co-workers.24 Sodium sulnate

Scheme 13 Metal-free, aerobic quinoline synthesis. Scheme 15 Synthesis of quinoline derivative 63.

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Scheme 16 Synthesis of quinoline 66 in water.

Scheme 20 Copper(II) triflate mediated synthesis of a quinoline
derivative.
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Scheme 21 Synthesis of 2-trifluoromethylquinoline.

reaction (Scheme 21). Chen and co-workers reported a novel

and efficient procedure for the synthesis of 2-tri-
Scheme 17 Synthesis of quinoline 69 through various reaction
conditions.
uoromethylquinolines 80 and 81 using copper-chloride salt
under aerobic reaction conditions with various functional
group tolerances.31
2,3-Disubstituted quinoline 84 was synthesized through
aminoaryl alcohol 72 and acyclic/cyclic ketones 73 or secondary
multicomponent coupling reactions of alkyne 83, amine 29 and
alcohol 74 via a sequential dehydrogenation and condensation
aldehyde 82 using a zinc(II) triate salt catalyst (Scheme 22).32
reaction process (Scheme 19).29 The advantage of conducting
The merits of this procedure are that reactions can proceed
reactions via this method is that it uses a simple-to-handle and
without the presence of ligands or co-catalysts, under solvent-
inexpensive nickel(II) catalyst. Luo and co-workers reported 6-
free and inert reaction conditions. Bao and co-workers
chloro-2-dimethyl-4-phenylquinoline, an antiparasitic agent,
recently reported a simple and efficient synthetic protocol for
and 3,4-diphenylquinoline-2(1H)-one, a p38aMAP kinase
the construction of sulfonylated quinoline in water via a zinc
inhibitor, as biologically active quinoline derivatives. The
powder mediated coupling reaction.33
reaction proceeds through a single-step process and under
Haloquinolines 85 and 86 reacted with sulfonyl chloride in
neutral reaction conditions using a copper triate catalyst in
water in the presence of cheap metal zinc powder to afford
nitromethane.30 In contrast to an acid-catalysed two-step [4 + 2]
sulfonylated quinolines 87 and 88, respectively (Scheme 23).
cycloaddition and oxidation reaction, it allows a single-step
Mondal and co-workers reported a neat ZnII/CuI catalyzed
reaction to provide quinoline in high yields and excellent
reaction procedure to synthesise quinoline 91 through the
regioselectivity (Scheme 20). N-(2-alkenylaryl)enamine 79 is
uncommon sp2 C–H activation of three-component protocols.34
a strategic precursor for the synthesis of quinoline 80 or 81
Aniline 29, alkynes 89 and aldehydes 90 react via a cascade
using a one-pot copper-catalysed aerobic oxidative cyclization
cyclization reaction to provide quinoline 91 (Scheme 24).

Scheme 18 Cobalt-catalysed synthesis of quinoline derivatives.

Scheme 22 Zinc triflate mediated synthesis of quinoline derivatives.

Scheme 23 Zinc powder mediated synthesis of sulfonylated quinoline

Scheme 19 Nickel-catalysed synthesis of polysubstituted quinolines. derivatives.

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Scheme 24 Copper–zinc combo-catalysed synthesis of quinoline

derivatives.
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2-Substituted quinoline 97 is prepared from either 2-ami- Scheme 26 Silver triflate mediated synthesis of polysubstituted
nobenzyl alcohol and alkyne/ketone or 2-aminophenethyl quinolines.
alcohol and aldehyde using an AgOTf catalyst.35 Synthetically
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important heterocyclic anchored quinolines, such as furan,

3.1. Antibacterial activity
pyrrole and thiophene, can be synthesized via a facile and
economic procedure using a silver triate catalyst in toluene Desai and co-workers reported the synthesis of quinoline
solvent with commercially available precursors and additives, derivatives 107, 108 and 109 exhibiting the most powerful
as reported by Xu and co-workers (Scheme 25). Aerwards, the antimicrobial activities (Fig. 3).50 The synthesized compounds
silver triate catalysed one-step synthesis of quinoline with were screened for their potential antibacterial activity on
a broad scope of substrates was reported by Xu and co- Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli,
workers.36 and Pseudomonas aeruginosa using ampicillin as a standard
Multicomponent reactions proceeding using aniline 37, drug. The recorded results revealed that these compounds have
aldehyde 98, and ketones 99 or 100 reacting in the presence of good bacterial activity with minimum inhibition concentrations
a silver triate catalyst provide quinolines 101 or 102 (Scheme of 12.5 mg ml 1 and 50 mg ml 1. Furthermore, the authors claim
26). that the potential activity of these compounds is directly asso-
Xie and co-workers reported an effective and suitable ciated with the substituent effect on the ring. These three
protocol for the synthesis of 2-aminoquinoline 104 using an bioactive quinoline derivatives are linked using hydrazone, as
AgBF4 catalyst in DMF solvent.37 The reaction proceeds using reported by Le and co-workers.51 Quinoline derivatives with
isothiocyanate 103 under basic and oxidant-free mild reaction a hydrazone linker 110, 111 and 112 showed good growth
conditions to provide good to excellent yields (Scheme 27). inhibition of targeted bacteria.
The reaction of commercially available starting materials Furthermore, Fu and co-workers synthesized hybridized
aniline 14 and aryl allyl alcohol 105 using a palladium acetate quinoline derivative 113 with a piperazine moiety linker and
catalyst in DMSO solvent via an oxidative cyclization reaction reported that it showed broad-spectrum antibacterial activities
provides quinoline 106 (Scheme 28).38 It does not need to on selected bacteria with MIC values of 0.125–8 mg ml 1.52
employ any acid, base or additive to promote the reaction. The
procedure works with a broad scope of substrates and strong 3.2. Antioxidant activity
electron-withdrawing substituted materials to furnish moderate Bazine and co-workers report that quinoline derivative 114
to satisfactory yields. anchored with an a-aminophosphate revealed effective antiox-
idant activity when compared with standard DPPH (Fig. 4).53
3. Bioactivities of quinolines The authors conrmed that the bioactivity was further modied
through the introduction of a phenol ring as a substituent to the
Both natural products and synthetic compounds which are quinoline scaffold.
anchored with a quinoline scaffold have certainly exhibited
a broad range of biological or pharmaceutical activities.39,40 3.3. Anticancer activity
Among them are antibacterial,41,42 antioxidant,43 anticancer,44
Bingul and co-workers synthesized and reported quinoline
anti-inammatory,45,46 antimalarial,47,48 and antifungal activities.49
derivative 115 for anticancer activity against neuroblastoma cells
(Fig. 5). The authors revealed that compound 115 showed
reasonable anticancer activities against SH-SY5Y and Kelly
neuroblastoma cell lines and decreased the viability of neuro-
cancer cells with substantial selectivity over normal cells.54
Compounds 117 and 118 are quinoline derivatives anchored with

Scheme 25 Silver triflate catalysed synthesis of quinoline derivatives. Scheme 27 Silver-catalysed amination of quinoline N-oxides.

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Scheme 28 Palladium-catalysed synthesis of quinoline derivatives.

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Fig. 5 Chemical structures of anticancer active quinoline derivatives.

antileishmanial activity (Fig. 7).58 The authors revealed that

having a chloro-substituent enhanced the activity of the
synthesized compound.
Phosphorated quinoline 121 is a hybrid and potent anti-
leishmanial agent.59 Phosphorus hybridized with quinoline is
a promising basis for strong antileishmanial activity.

3.6. Antimalarial activity

Currently, scholars are exploring how to improve and enhance
the antimalarial activity of compounds with a quinoline scaffold.
These are mainly synthesized quinoline derivatives hybridized
with commercially available and potentially recognized drugs.60
Investigators claim that hybridization will result in benets of
cost-effectiveness and minimize the risk of drug–drug interac-
Fig. 3 Chemical structures of antibacterially active quinoline tion. Lombard and co-workers reported quinoline hybridized
derivatives.
with artemisinin drug and provided compound 122 (Fig. 8). The
hybrid compound exhibited antimalarial activity, although not as
a thiophene moiety, reported by Othman and co-workers.55 The much as dihydroartemisinin, but it showed excellent anti-
above quinolines exhibited powerful anticancer activity against plasmodial activity.61 The antimalarially active quinoline–
MCF-7 human cancer cells with IC50 values of 38.41 and 28.36 sulfonamide hybrid derivative 123 was synthesized and reported
mM, respectively. Additionally, Kundu and co-workers reported by Verma and co-workers.62 The authors revealed that the hybrid
that quinoline 116 with an imidazole and 1,3,4-oxadiazole compound exhibited inhibition of the formation of hemozoin.
exhibited the highest potency for human topoisomerase 1.56

3.7. Antifungal activity

3.4. Anti-inammatory activity
Antifungal active compounds 6-peruoropropanyl quinoline
Tseng and co-workers synthesized and reported indeno[1,2-c] 124 and 125 were synthesized and reported by Fang and co-
quinoline derivatives 119 as a potent anti-TB agent, besides workers (Fig. 9).63 The synthesized quinoline derivatives
being a potent anti-inammatory agent with low cytotoxicity exhibited excellent antifungal activity against Pyricularia oryzae.
(Fig. 6).57 El Shehry and co-workers synthesized and reported an anti-
fungally active pyrazole–quinoline hybrid 126 (Fig. 9).64 The
3.5. Antileishmanial activity
Upadhyay and co-workers synthesized and reported that quin-
oline derivative 120 anchored with a triazole exhibited

Fig. 6 Chemical structure of anti-inflammatory active quinoline

Fig. 4 Chemical structure of an antioxidant active quinoline derivative. derivative.

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exhibited a potentially wide range of applications to treat

various kinds of human infections, such as bacterial infections,
cancer, malaria and fungal infections. The above-mentioned
synthesis protocols based on green synthesis procedures are
usually suggested for preparing this noble organic compound
and its analogues.
Fig. 7 Chemical structure of antileishmanial active quinoline
derivative.
Conflicts of interest
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Article content has no conict of interest.

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