Design, Synthesis and Antimalarial Activity of Some New 2-Hydroxy-1,4-naphthoquinone-4-hydroxyaniline Hybrid Mannich Bases

Sharma, Dipshikha; Chetia, Dipak; Rudrapal, Mithun

doi:10.14233/ajchem.2016.19478

Cited by 23 publications

(25 citation statements)

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“…To a mixture of 2-hydroxy-1,4-naphthoquinone (7 g, 40 m/mol) and pyridine (3.2 g, 3.2 ml, 40 m/mol), thionyl chloride (6 ml) was added drop wise, and the resulting solution was heated under reflux at 70° for about 1 h. The solvent was removed under vacuum and the product thereby obtained was separated [11] .…”

Section: General Procedures Of Synthesismentioning

confidence: 99%

“…The organic solution was washed with water, dried over anhydrous sodium sulphate and then evaporated to dryness under reduced pressure to yield the crude product. The product was recrystallized from methanol [11,17] .…”

Section: General Procedures Of Synthesismentioning

confidence: 99%

“…The mean of percentage of inhibition of parasite growth was calculated for duplicate studies. Further, the minimum inhibitory concentration (MIC) and inhibitory concentration at 50% of maximal inhibition (IC 50 ) values (in µg/ml) were also calculated using the NonLin v1.1 software [11,[18][19][20] .…”

Section: In Vitro Antimalarial Activity Evaluationmentioning

confidence: 99%

“…The design of hybrid molecules therefore remains to be an effective alternative approach in rational drug design paradigm, which involves covalent fusion of two or more pharmacophore units into a single molecular entity with distinct pharmacodynamic property targeting multiple therapeutic targets [3,11,12] . A single hybrid molecule therefore exhibit improved therapeutic response just similar to synergistic like drug action.…”

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confidence: 99%

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Synthesis, Antimalarial Activity Evaluation and Drug likeness Study of Some New Quinoline-Lawsone Hybrids

Kashyap¹,

Chetia²,

Rudrapal³

2016

pharmaceutical-sciences

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Kashyap, et al.: Antimalarial Activity of Quinoline-Lawsone HybridsIn the present study, a new series of quinoline-lawsone hybrid compounds were synthesized and evaluated in vitro for their antimalarial effectiveness. Several aliphatic and aromatic/heteroaromatic diamines were used as connecting/bridge moiety between the 7-chloro-4-aminoquinoline and 3-amino-1, 4-naphthoquinone pharmacophoric scaffolds. The molecular properties of hybrid compounds were also studied in silico for drug-likeness assessment based on Lipinski's rule of five. Results of antimalarial activity reveal that all the tested compounds showed activity against both chloroquine sensitive (RKL-2) and chloroquine resistant (RKL-9) strains of Plasmodium falciparum which was considerably less as compared to the standard drug, chloroquine. All the compounds exhibited same degree of activity at the tested dose against sensitive strain with IC 50 values 0.391-1.033 µg/ml. Furthermore, four compounds which were additionally tested against resistant strain also showed activity with IC 50 values from 0.684 to 1.778 µg/ml at the same dose. The IC 50 values for CQ against sensitive and resistant strains of P. falciparum were found to be 0.0391 µg/ml and 0.305 µg/ml, respectively. From results it is apparent that the compound with a small alkyl bridge moiety diaminoethyl possesses better activity profile against both sensitive and resistant strains (IC 50 =0.391 and 0.684 µg/ml, respectively) than rest of the synthesized analogues. The results of drug-likeness studies showed that all newly designed quinoline-lawsone hybrids possess good drug-like properties, indicating their druglikeness behaviour is favourable for optimal antimalarial action. Assessment of drug-likeness score further implies the suitability of hybrid derivatives as drug-like molecules.Key words: Quinoline, lawsone, hybrid, bridge moiety, Plasmodium falciparum, resistant malariaOver the last few decades, the burden of malaria has increasingly become a serious health concern around the globe. The disease remains one of the most lethal infectious diseases of human beings affecting around 300-600 million people with about three million deaths per year globally [1] . Plasmodium falciparum is the most prevalent and deadly species among all malaria parasites, which causes severe complicated malaria such as cerebral malaria, and is responsible for most of the malaria-related deaths worldwide. Recent emergence of multidrug-resistant strains of P. falciparum has further complicated the issues of treating malaria using currently available antimalarial drugs [2][3][4] . However, with the development of novel and potent antimalarial agents the above challenging issue could be addressed.Chloroquine (CQ, fig. 1), a 4-aminoquinoline synthetic antimalarial, was once a highly potent drug against malaria. Literature reports suggest that 7-chloro-4-aminoquinoline nucleus of 4-aminoquinoline antimalarial drugs is responsible for their antimalarial action which could be attributed mainly due to the prevention o...

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Section: General Procedures Of Synthesismentioning

confidence: 99%

Section: General Procedures Of Synthesismentioning

confidence: 99%

Section: In Vitro Antimalarial Activity Evaluationmentioning

confidence: 99%

mentioning

confidence: 99%

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Synthesis, Antimalarial Activity Evaluation and Drug likeness Study of Some New Quinoline-Lawsone Hybrids

Kashyap¹,

Chetia²,

Rudrapal³

2016

pharmaceutical-sciences

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“…Chloroquine (0.1 mg/ml) was used as the standard reference drug. 15,16 Test results were compared with the standard result of CQ. Each test compound was assayed in three replicates and counted against 200 asexual parasites (% dead rings+trophozoites) per replicate.…”

Section: Antimalarial Activity Evaluationmentioning

confidence: 99%

Synthesis and Antimalarial Activity Evaluation of Some Mannich Bases of Tetraoxane-Phenol Conjugate

Jinky¹,

Chetia²,

Mukesh³

et al. 2016

IJPER

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A new series of seven Mannich bases of tetraoxane-phenol conjugate as possible antimalarial compounds were synthesized and evaluated in vitro for their antimalarial activity. All the synthesized compounds exhibited good antimalarial activity against the CQ-sensitive strain (RKL-2) of P. falciparum. Compounds with 3-indolyl and phenolic substituent's showed considerably superior activity than rest of the synthesized tetraoxane derivatives in the series, with IC 50 values 8.19 µg/ml and 5.30 µg/ml, respectively. The activity was, however, less than that of the standard reference drug, CQ (IC 50 0.04 µg/ml). Three selected compounds were also screened for the activity against a CQresistant strain (RKL-9) of P. falciparum, which was also found good with IC 50 values 41.77 µg/ml, 39.87 µg/ml and 34.59 µg/ml for compounds having phenyl, furan-2-yl and 4-pyridyl substituent's, respectively in the Mannich base component of the conjugated tetraoxane-phenol scaffold. The activity against CQ-sensitive strain of P. falciparum was better as compared to the activity seen against resistant strain. Results clearly indicate that Mannich bases of tetraoxane-phenol conjugate with bulky aromatic/heteroaromatic groups possess antimalarial potential both against CQ-sensitive and -resistant strains of P. falciparum.

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1,4‐Naphthoquinone: A Privileged Structural Framework in Drug Discovery

Dar¹,

Kamal²,

Shah³

2021

Chemistry of Biologically Potent Natural Products and Synthetic Compounds

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Design, Synthesis and Antimalarial Activity of Some New 2-Hydroxy-1,4-naphthoquinone-4-hydroxyaniline Hybrid Mannich Bases

Cited by 23 publications

References 0 publications

Synthesis, Antimalarial Activity Evaluation and Drug likeness Study of Some New Quinoline-Lawsone Hybrids

Synthesis, Antimalarial Activity Evaluation and Drug likeness Study of Some New Quinoline-Lawsone Hybrids

Synthesis and Antimalarial Activity Evaluation of Some Mannich Bases of Tetraoxane-Phenol Conjugate

1,4‐Naphthoquinone: A Privileged Structural Framework in Drug Discovery

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