One‐Pot Laccase‐Catalysed Synthesis of 5,6‐Dihydroxylated Benzo[b]furans and Catechol Derivatives,and Their Anticancer Activity

A commercial laccase, Suberase® from Novozymes, was used to catalyse the synthesis of 5,6‐dihydroxylated benzo[b]furans and catechol derivatives. The yields were, in some cases, similar to or better than that obtained by other enzymatic, chemical or electrochemical syntheses. The synthesised derivatives were screened against renal (TK10), melanoma (UACC62), breast (MCF7) and cervical (HeLa) cancer cell lines. GI₅₀, TGI and LC₅₀ are reported for the first time. Anticancer screening showed that the cytostatic effects of the 5,6‐dihydroxylated benzo[b]furans were most effective against the melanoma (UACC62) cancer cell line with several compounds exhibiting potent growth inhibitory activities (GI₅₀ = 0.77–9.76 µM), of which two compounds had better activity than the anticancer agent etoposide (GI₅₀ = 0.89 µM). One compound exhibited potent activity (GI₅₀ = 9.73 µM) against the renal (TK10) cancer cell line and two exhibited potent activity (GI₅₀ = 8.79 and 9.30 µM) against the breast (MCF7) cancer cell line. These results encourage further studies of the 5,6‐dihydroxylated benzo[b]furans for their potential application in anticancer therapy.     

Exploration of imidazole and imidazopyridine dimers as anticancer agents: Design,synthesis, and structure–activity relationship study

Dimerization of proteins/receptors plays a critical role in various cellular processes, including cell proliferation and differentiation. Therefore, targeting such dimeric proteins/receptors by dimeric small molecules could be a potential therapeutic approach to treating various diseases, including inflammation‐associated diseases like cancer. A novel series of bis‐imidazoles ( 13–18 ) and bis‐imidazo[1,2‐a]pyridines ( 19–28 ) were designed and synthesized from Schiff base dimers ( 1–12 ) for their anticancer activities. All the synthesized compounds were screened for anticancer activities against three cancer cell lines, including cervical (HeLa), breast (MDA‐MB‐231), and renal cancer (ACHN). From structure–activity relationship studies, imidazo[1,2‐a]pyridines ( 19–28 ) showed remarkable cytotoxic activities, with compounds 19 and 24 showing the best inhibitory activities against all three cell lines. Especially, both 19 and 24 were very effective against the breast cancer cell line ( 19 , GI₅₀ = 0.43 µM; 24 , GI₅₀ = 0.3 µM), exceeding the activity of the control adriamycin (GI₅₀ = 0.51 µM). The in vivo anticancer activity results of compounds 19 and 24 were comparable with those of the animals treated with the standard drug tamoxifen. Therefore, the dimeric imidazo[1,2‐a]pyridine scaffold could serve as a potential lead for the development of novel anticancer agents.     

Bioassay‐Guided Isolation and Structural Modification of the Anti‐TB Resorcinols from Ardisia gigantifolia

Tuberculosis (TB) is a highly contagious disease mainly caused by Mycobacterium tuberculosis H₃₇R_V. Antitubercular (anti‐TB) bioassay‐guided isolation of the CHCl₃ extract of the leaves and stems of the medicinal plant Ardisia gigantifolia led to the isolation of two anti‐TB 5‐alkylresorcinols, 5‐(8Z‐heptadecenyl) resorcinol ( 1 ) and 5‐(8Z‐pentadecenyl) resorcinol ( 2 ). We further synthesized 15 derivatives based on these two natural products. These compounds (natural and synthetic) were evaluated for their anti‐TB activity against Mycobacterium tuberculosis H₃₇R_V. Resorcinols 1 and 2 exhibited anti‐TB activity with MIC values at 34.4 and 79.2 μm in MABA assay, respectively, and 91.7 and 168.3 μm in LORA assay, respectively. Among these derivatives, compound 8 was found to show improved anti‐TB activity than its synthetic precursor ( 2 ) with MIC values at 42.0 μm in MABA assay and 100.2 μm in LORA assay. The active compounds should be regarded as new hits for further study as a novel class of anti‐TB agents. The distinct structure–activity correlations of the parent compound were elucidated based on these derivatives.     

Design and synthesis of new 2‐anilinoquinolines bearing N‐methylpicolinamide moiety as potential antiproliferative agents

A series of new 2‐anilinoquinolines 6a – o possessing the substantial N‐methylpicolinamide motif at C5 has been designed and synthesized as sorafenib analogs. The antiproliferative activities of the target compounds were preliminarily appraised against a panel of three human cancer cell lines (MCF‐7, SK‐BR3, and HCT116), and a selected array was further tested over a panel of approximately 60 cancer cell lines at NCI at 10 μM concentration. Interestingly, compounds 6c , 6d , 6j , 6k , and 6l showed promising selective anticancer activities (growth inhibition >80%) toward certain cancer cells at 10 μM testing dose. Compounds 6d and 6j were advanced to five‐dose testing mode to determine their GI₅₀ values and compared with our previously reported ureidoquinoline B and sorafenib as reference compounds. The 4‐chloro‐3‐trifluoromethylaniline derivative 6j manifested superior potency than both compound B and sorafenib over eleven and eight cell lines, respectively. It showed GI₅₀ values of 0.36, 0.66, 0.68, and 0.60 μM against the breast MDA‐MB‐468, renal A498, and melanoma SK‐MEL‐5 and UACC‐62 cell lines, respectively. Moreover, both 6d and 6j exerted low cytotoxic effects against HFF‐1 normal cell line. Furthermore, compounds 6d and 6j were tested against both B‐Raf^V600E and C‐Raf kinases and displayed modest inhibitory activities, which were justified by molecular docking study. Compound 6j could serve as a promising candidate for further development of potent anticancer chemotherapeutics.     

Synthesis and biological evaluation of novel imidazopyrimidin‐3‐amines as anticancer agents

Groebke–Blackburn–Bienayme reaction has been utilized for the synthesis of new imidazo[1,2‐a]pyrimidine derivatives as novel anticancer agents. The cytotoxic activities of compounds were evaluated against human cancer cell lines including MCF‐7, T‐47D, and MDA‐MB‐231, compared with etoposide as the standard drug. Among the tested compounds, hydroxy‐ and/or methoxy‐phenyl derivatives ( 6a–c and 6k ) with IC₅₀ values of 6.72–14.36 μm were more potent than etoposide against all cell lines. The acridine orange/ethidium bromide double staining and DNA fragmentation studies demonstrated that the cytotoxic effect of 3‐hydroxy‐4‐methoxyphenyl derivative 6c is associated with apoptosis in cancer cells.     

Synthesis and evaluation of pyridinium‐hydrazone derivatives as potential antitumoral agents

The hydrazones of 4‐hydrazinylpyridinium bearing alkylphenyl groups on pyridinium nitrogen were synthesized and evaluated for their cytotoxic activity against MCF‐7, PC3, U2OS, and HEK293 cell lines by Wst1 cell proliferation assay. Cytotoxic activity results indicated that d derivatives having butylene chain; 4 and 5 series having naphthalene and anthracene ring systems showed high cytotoxic activity (IC₅₀ = 3.27–8.54 μm ) on cancer cells. 3d (4‐(2‐(4‐hydroxybenzylidene)hydrazinyl)‐1‐(4‐phenylbutyl)pyridinium bromide) was the most cytotoxic compound with IC₅₀ value of 3.27 μm against MCF‐7. The most active derivatives ( 1d , 2d , 3d , 4 , and 5 series) were selected to investigate for the effects on autophagy by analyzing the expression of autophagy marker proteins. The conversion of LC3‐I to its lipidated form LC3‐II is essential for autophagy and related to autophagosomes. According to our results, all tested compounds except for 3d induced lipidated form LC3‐II accumulation. Then, the effects of the compounds on p62 protein level were also analyzed by the immunoblotting as the autophagy inhibition results in accumulation of p62. Further molecular mechanistic studies including morphological analysis and live–death assays indicated that all tested compounds ( 1d , 2d , 3d , 4 , and 5 series) are potent antitumoral molecules and all except for 3d have potential to inhibit autophagic flux.     

Design,Synthesis, and Biological Evaluation of 1‐(thiophen‐2‐yl)‐9H‐pyrido[3,4‐b]indole Derivatives as Anti‐HIV‐1 Agents

A novel series of 1‐(thiophen‐2‐yl)‐9H‐pyrido [3,4‐b]indole derivatives were synthesized using DL‐tryptophan as starting material. All the compounds were characterized by spectral analysis such as ¹H NMR, Mass, IR, elemental analysis and evaluated for inhibitory potency against HIV‐1 replication. Among the reported analogues, compound 7g exhibited significant anti‐HIV activity with EC₅₀ 0.53 μm and selectivity index 483; compounds 7e , 7i , and 7o displayed moderate activity with EC₅₀ 3.8, 3.8, and 2.8 μm and selectivity index >105, >105, and 3.85, respectively. Interestingly, compound 7g inhibited p24 antigen expression in acute HIV‐1_IIIB infected cell line C8166 with EC₅₀ 1.1 μm . In this study, we also reported the Lipinski rule of 5 parameters, predicted toxicity profile, drug‐likeness, and drug score of the synthesized analogues.     

Synthesis and Structure‐Activity Relationship Studies of Pyrazole‐based Heterocycles as Antitumor Agents

Several 4‐cyano‐1,5‐diphenylpyrazoles attached to different heterocyclic ring systems at position 3 were synthesized starting from ethyl 4‐cyano‐1,5‐diphenyl‐1H‐pyrazole‐3‐carboxylate 1 . The newly synthesized compounds were tested in vivo for their anti‐estrogenic effects and evaluated in vitro for their cytotoxic properties against estrogen‐dependent tumors. 3‐(5‐Mercapto‐1,3,4‐oxadiazole‐2‐yl)‐1,5‐diphenyl‐1H‐pyrazole‐4‐carbonitrile 13 revealed the highest cytotoxic activity with a GI₅₀ value equal to 40 nM against the IGROVI ovarian tumor cell line. It also showed an anti‐estrogen activity 1.6 more effective than the reference drug, in addition to a high tolerable dose. 3‐(5‐(Methylthio)‐4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1,5‐diphenyl‐1H‐pyrazole‐4‐carbonitrile 7 was found to have the highest anti‐estrogenic activity, while 1,5‐diphenyl‐3‐[5‐(phenylamino)‐1,3,4‐thiadiazol‐2‐yl]‐1H‐pyrazole‐4‐carbonitrile 11 showed the lowest activity. The oral LD₅₀ values revealed that most of the tested compounds are relatively nontoxic.     

Synthesis and Biological Evaluation of a Series of 2‐((1‐substituted‐1H‐1,2,3‐triazol‐4‐yl)methylthio)‐6‐(naphthalen‐1‐ylmethyl)pyrimidin‐4(3H)‐one As Potential HIV‐1 Inhibitors

A series of novel S‐DABO derivatives with the substituted 1,2,3‐triazole moiety on the C‐2 side chain were synthesized using the simple and efficient CuAAC reaction, and biologically evaluated as inhibitors of HIV‐1. Among them, the most active HIV‐1 inhibitor was compound 4‐((4‐((4‐(2,6‐dichlorobenzyl)‐5‐methyl‐6‐oxo‐1,6‐dihydropyrimidin‐2‐ylthio)methyl)‐1H‐1,2,3‐triazol‐1‐yl)methyl)benzenesulfonamide ( B5b7) , which exhibited similar HIV‐1 inhibitory potency (EC₅₀ = 3.22 μm ) compared with 3TC (EC₅₀ = 2.24 μm ). None of these compounds demonstrated inhibition against HIV‐2 replication. The preliminary structure–activity relationship (SAR) of these new derivatives was discussed briefly.     

Synthesis,biological evaluation,and molecular docking studies of novel 3‐aryl‐5‐(alkyl‐thio)‐1H‐1,2,4‐triazoles derivatives targeting Mycobacterium tuberculosis

A small library of new 3‐aryl‐5‐(alkyl‐thio)‐1H‐1,2,4‐triazoles was synthesized and screened for the antimycobacterial potency against Mycobacterium tuberculosis H₃₇Ra strain and Mycobacterium bovis BCG both in active and dormant stage. Among the synthesized library, 25 compounds exhibited promising anti‐TB activity in the range of IC₅₀0.03–5.88 μg/ml for dormant stage and 20 compounds in the range of 0.03–6.96 μg/ml for active stage. Their lower toxicity (>100 μg/ml) and higher selectivity (SI = >10) against all cancer cell lines screened make them interesting compounds with potential antimycobacterial effects. Furthermore, to rationalize the observed biological activity data and to establish a structural basis for inhibition of M. tuberculosis, the molecular docking study was carried out against a potential target MTB CYP121 which revealed a significant correlation between the binding score and biological activity for these compounds. Cytotoxicity and in vivo pharmacokinetic studies suggested that 1,2,4‐triazole analogues have an acceptable safety index, in vivo stability and bio‐availability.     

Design,synthesis, and molecular docking studies of N‐(9,10‐anthraquinone‐2‐carbonyl)amino acid derivatives as xanthine oxidase inhibitors

A series of N‐(9,10‐anthraquinone‐2‐carbonyl)amino acid derivatives ( 1a–j ) was designed and synthesized as novel xanthine oxidase inhibitors. Among them, the L/D‐phenylalanine derivatives ( 1d and 1i ) and the L/D‐tryptophan derivatives ( 1e and 1j ) were effective with micromolar level potency. In particular, the L‐phenylalanine derivative 1d (IC₅₀ = 3.0 μm ) and the D‐phenylalanine derivative 1i (IC₅₀ = 2.9 μm ) presented the highest potency and were both more potent than the positive control allopurinol (IC₅₀ = 8.1 μm ). Preliminary SAR analysis pointed that an aromatic amino acid fragment, for example, phenylalanine or tryptophan, was essential for the inhibition; the D‐amino acid derivative presented equal or greater potency compared to its L‐enantiomer; and the 9,10‐anthraquinone moiety was welcome for the inhibition. Molecular simulations provided rational binding models for compounds 1d and 1i in the xanthine oxidase active pocket. As a result, compounds 1d and 1i could be promising lead compounds for further investigation.     

Synthesis and Cytotoxic Evaluation of 6‐(3‐Pyrazolylpropyl) Derivatives of 1,4‐Naphthohydroquinone‐1,4‐diacetate

Several new 6‐(3‐pyrazolylpropyl) derivatives of 1,4‐naphthohydroquinone‐1,4‐diacetate (NHQ‐DA) have been prepared by chemical modifications of the Diels–Alder adduct of α‐myrcene and 1,4‐benzoquinone. All these new compounds and precursors have been evaluated in vitro for their cytotoxicity against cultured human cancer cells of MB‐231 breast‐adeno carcinoma, A‐549 lung carcinoma, and HT‐29 colon carcinoma. GI₅₀ values ranged in and below the micromolar concentration level.     

Design,synthesis and cytotoxic evaluation of nitric oxide‐releasing derivatives of isosteviol

Twenty‐six novel isosteviol derivatives coupled with two types of nitric oxide (NO) donors (furoxans and NONOates) were synthesized and screened for cytotoxic activities against four human cancer cell lines with sunitinib as the positive control. The results showed that seven furoxan‐based derivatives ( 8a , 8b , 8c , 8d , 8e , 9e , and 9f ) exhibited desirable cytotoxic activities, while NONOate‐based derivatives displayed poor potency because of unstability. Compared with sunitinib, compounds 8a and 8e were more active on all tested cell lines, especially in HCT116 ( 8a , IC₅₀ = 0.48 ± 0.02 μm ; 8e , IC₅₀ = 0.94 ± 0.01 μm ); compounds 8b and 8d were more potent on HCT116 (IC₅₀ = 3.39 ± 0.06 and 3.29 ± 0.03 μm ), HepG2 (IC₅₀ = 1.05 ± 0.03 and 5.37 ± 0.08 μm ), and SW620 (IC₅₀ = 1.33 ± 0.02 and 4.11 ± 0.05 μm ) cell lines, and 8c exhibited higher activities on HepG2 cells with an IC₅₀ = 4.76 ± 0.14 μm . NO‐releasing experiment of compounds 8a – e , 17a , 18a , 19a , and 21a reminded us that NO‐releasing amount of this series of isosteviol derivatives positively correlates with their cytotoxic activities.     

Lipophilic conformationally constrained spiro carbocyclic 2,6‐diketopiperazine‐1‐acetohydroxamic acid analogues as trypanocidal and leishmanicidal agents: An extended SAR study

We have previously described a number of lipophilic conformationally constrained spiro carbocyclic 2,6‐diketopiperazine (2,6‐DKP)‐1‐acetohydroxamic acids as potent antitrypanosomal agents. In this report, we extend the SAR analysis in this class of compounds with respect to in vitro growth inhibition of Trypanosoma and Leishmania parasites. Introduction of bulky hydrophobic substituents at the vicinal position of the basic nitrogen atom in the spiro carbocyclic 2,6‐DKP ring system can provide analogues which are potently active against bloodstream form Trypanosoma brucei and exhibit significant activities toward Trypanosoma cruzi epimastogotes and Leishmania infantum promastigotes and intracellular amastigotes. In particular, compounds possessing a benzyl or 4‐chlorobenzyl substituent were found to be the most active growth inhibitors, with activities in the low nanomolar and low micromolar ranges for T. brucei and L. infantum, respectively. The benzyl‐substituted (S)‐enantiomer was the most potent derivative against T. brucei (IC₅₀ = 6.8 nm ), T. cruzi (IC₅₀ = 0.21 μm ), and L. infantum promastigotes (IC₅₀ = 2.67 μm ) and intracellular amastigotes (IC₅₀ = 2.60 μm ). Moreover, the (R)‐chiral benzyl‐substituted derivative and its racemic counterpart displayed significant activities against L. donovani. Importantly, the active compounds show high selectivity in comparison with two mammalian cell lines.     

Design,Synthesis and Bioevaluation of Novel N‐Substituted‐3,5‐Bis(Arylidene)‐4‐piperidone Derivatives as Cytotoxic and Antitumor Agents with Fluorescent Properties

Ten new N‐substituted‐3,5‐bis(arylidene)‐4‐piperidone derivatives (series 1 and 2 ) were synthesized and subsequently evaluated against human carcinoma cell lines SW1990, MIA PaCa‐2, PG‐BE1, NCI‐H460, and SK‐BR‐3 for cytotoxic activity by the CCK‐8 method, and their fluorescent properties were investigated as well. The compounds were confirmed to display greater cytotoxic activity to the neoplastic cells, and approximately 50% of the IC₅₀ values were lower than 5 μm . In particular, compounds 1a , 1c , 1d, and 1e bearing 3‐bromophenyl groups were revealed as the most active antitumor drug candidates and had the average IC₅₀ values of 1.94, 1.11, 1.16, and 0.817 μm , respectively. Furthermore, their fluorescent properties were interesting and might contribute to the visualization of their distribution in tumor cells. Some possible reasons for the disparity between cytotoxic activity and fluorescent properties in the two series of compounds were explored. This study revealed high potential of these molecules for further development as fluorescent cytotoxic and antitumor agents.     

Elaborating on efficient anti-proliferation agents of cancer cells and anti-inflammatory-based N-bisphosphonic acids

Methylenebisphosponic acid tetraethyl ester ( 1 ) was added to 2‐azido‐ 7a–e and 2‐chloroquinoline‐3‐chalcones 10a–e in boiling sodium ethanolate solution to give, via Michael addition, tetrazolo[1,5‐a]quinoline‐ 8a–d , 13a and 2‐chloroquinoline‐based bisphosphonates 11a–d , 14a in E‐configuration. Further acid hydrolysis afforded the respective BP‐acid analogues E‐ 9a–d , 12a–d , 13b , and 14b in excellent yields. Anti‐tumor activity screening for the new BP‐acids at a dose of 10 µM utilizing 44 different human tumor cell lines representing breast, ovary, prostate, lung, and CNS cancer as well as leukemia and melanoma was carried out. Eight of ten tested compounds exhibited remarkable anti‐tumor activity against breast and prostate cancer, and a promising anti‐tumor sensitivity toward ovarian cancer and melanoma. Conversely, there was only scattered activity against leukemia and no noticeable action of these BP‐acids on CNS or lung cancer. Based on the prediction results (PASS program), anti‐inflammatory activity of the new acids was also determined in vivo, by the acute carrageenin induced paw edema in rats. Many of these compounds showed anti‐inflammatory properties at a dose of 50 mg/kg body weight.     

Novel peptidomimetic peptide deformylase (PDF) inhibitors of Mycobacterium tuberculosis

Emergence of MDR‐TB and XDR‐TB led to the failure of available anti‐tubercular drugs. In order to explore, identify and develop new anti‐tubercular drugs, novel peptidomimetic series of Mtb–peptide deformylase (PDF) inhibitors was designed and synthesized. In vitro antimycobacterial potential of compounds was established by screening of compounds against Mycobacterium tuberculosis H37Rv strain using MABA. Among them, ester series of compounds 4a , 4b , 4c , 4d , and 4e were found most active, with compound 4c being highly active and exhibiting minimum inhibitory concentration of 6.25 µg/ml against M. tb H37Rv strain. Additionally, the compounds were docked to determine the probable binding interactions and understand the mechanism of action of most active molecules on Mtb‐peptide deformylase (PDF), which is involved in the mycobacterium protein synthesis.     

Synthesis,in Vitro,and in Vivo Biological Evaluation and Molecular Docking Analysis of Novel 3‐(3‐oxo‐substitutedphenyl‐3‐)4‐(2‐(piperidinyl)ethoxy)phenyl)propyl)‐2H‐chromen‐2‐one Derivatives as Anti‐breast Cancer Agents

The analogs of coumarin–chalcones have been reported to exhibit antineoplastic, anti‐allergic, antihepatoprotective, and estrogenic activity. Herein, we have reported 3‐(3‐oxo‐substitutedphenyl‐3‐)4‐(2‐(piperidinyl)ethoxy)phenyl)propyl)‐2H‐chromen‐2‐one derivatives as a new class of compounds that exhibit selectivity for ER‐α binding along with antiproliferative and cytotoxic activity on human breast cancer cell line. The active compounds which show prominent activity against estrogen receptor‐alpha‐positive (ER+) human breast cancer cell lines MCF‐7 and Zr‐75‐1 are subjected to in vivo screening. The Glide XP docking was performed for designed scaffold to optimize its structural requirement for ER‐α inhibition.     

Design and synthesis of 9H‐fluorenone based 1,2,3‐triazole analogues as Mycobacterium tuberculosis InhA inhibitors

We prepared fifty various 9H‐fluorenone based 1,2,3‐triazole analogues varied with NH, –S–, and –SO₂– groups using click chemistry. The target compounds were characterized by routine analytical techniques, ¹H, ¹³CNMR, mass, elemental, single‐crystal XRD ( 8a ) and screened for in vitro antitubercular activity against Mycobacterium tuberculosis (MTB) H37Rv strain and two “wild” strains Spec. 210 and Spec. 192 and MIC₅₀ was determined. Further, the compounds were evaluated for MTB InhA inhibition study as well. The final analogues exhibited minimum inhibitory concentration (MIC) ranging from 52.35 to >295 μm . Among the –NH– analogues, one compound 5p (MIC 58.34 μm ), among –S– containing analogues four compounds 8e (MIC 66.94 μm ), 8f (MIC 74.20 μm ), 8g (MIC 57.55 μm ), and 8q (MIC 56.11 μm ), among –SO₂– containing compounds one compound 10p (MIC 52.35 μm ) showed less than MTB MIC 74.20 μm : Compound 4‐(((9H‐fluoren‐9‐yl)sulfonyl)methyl)‐1‐(3,4,5‐trimethoxyphenyl)‐1H‐1,2,3‐triazole ( 10p ) was found to be the most active compound with 73% InhA inhibition at 50 μm ; it inhibited MTB with MIC 52.35 μm . Further, 10f and 10p were docked to crystal structure of InhA to know binding interaction pattern. Most active compounds were found to be non‐cytotoxic against HEK 293 cell lines at 50 μm .     

New Compounds Hybrids 1H‐1,2,3‐Triazole‐Quinoline Against Plasmodium falciparum

Malaria is one of the most prevalent parasitic diseases in the world. The global importance of this disease, current vector control limitations, and the absence of an effective vaccine make the use of therapeutic antimalarial drugs the main strategy to control malaria. Chloroquine is a cost‐effective antimalarial drug with a relatively robust safety profile, or therapeutic index. However, chloroquine is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of chloroquine‐resistant strains, which have also been reported for Plasmodium vivax. However, the activity of 1,2,3‐triazole derivatives against chloroquine‐sensitive and chloroquine‐resistant strains of P. falciparum has been reported in the literature. To enhance the anti‐P. falciparum activity of quinoline derivatives, we synthesized 11 new quinoline‐1H‐1,2,3‐triazole hybrids with different substituents in the 4‐positions of the 1H‐1,2,3‐triazole ring, which were assayed against the W2‐chloroquine‐resistant P. falciparum clone. Six compounds exhibited activity against the P. falciparum W2 clone, chloroquine‐resistant, with IC₅₀ values ranging from 1.4 to 46 μm . None of these compounds was toxic to a normal monkey kidney cell line, thus exhibiting good selectivity indexes, as high 351 for one compound ( 11 ).