Current development of β-carboline derived potential antimalarial scaffolds

Kushwaha, Preeti; Kumar, Vipin; Saha, Biswajit

doi:10.1016/j.ejmech.2023.115247

Cited by 10 publications

(4 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fortunately, it was inactive against non-tumor cells. UT harmiquine (8), prepared at O-7, was inactive, whereas TT (18,19) and AT (25) harmiquins showed significant non-selective activity. Surprisingly, the most active compound prepared at the N-9 position of the b-carboline was UT harmiquine 12, followed by TT harmiquins 20 and 21, and in the third place AT harmiquins 27 and 28.…”

Section: Antiproliferative Activitymentioning

confidence: 97%

“…Most of the modifications could be divided into several groups: 1) substitutions at positions 1, 2, 3, 6, and 9 of the b-carboline core, resulting in mono, di-and trisubstituted b-carbolines, 2) dimerization of b-carbolines employing various spacers resulting in bivalent b-carbolines, 3) hybridization of b-carbolines with other biologically active scaffolds and 4) preparation of b-carboline-based metal complexes (ruthenium(II), rhenium(I), copper(II), nickel(II), iridium (II)) (12)(13)(14)(15)(16)(17)(18). Different biological targets and mechanisms of anticancer and antimalarial action were explored, for example, DNA intercalation or groove binding, enzyme inhibition (topoisomerase, kinases, such as DYRK1A, haspin kinase and cyclin-dependent kinases, histone deacetylase, Pf phosphodiesterase, PfATP4), PfHsp90 and others (14,15,17,18). As already stated above, standard-of-care for both cancer and malaria includes drug combinations, although drug-drug interactions and lower treatment adherence could pose a problem for successful therapy.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Synthesis, antiproliferative and antiplasmodial evaluation of new chloroquine and mefloquine-based harmiquins

Pavić,

Poje,

Carvalho

et al. 2023

Acta Pharmaceutica

View full text Add to dashboard Cite

Here we present the synthesis and evaluation of the biological activity of new hybrid compounds, ureido-type (UT) harmiquins, based on chloroquine (CQ) or mefloquine (MQ) scaffolds and β-carboline alkaloid harmine against cancer cell lines and Plasmodium falciparum. The hybrids were prepared from the corresponding amines by 1,1′-carbonyldiimidazole (CDI)-mediated synthesis. In vitro evaluation of the biological activity of the title compounds revealed two hit compounds. Testing of the antiproliferative activity of the new UT harmiquins, and previously prepared triazole-(TT) and amide-type (AT) CQ-based harmiquins, against a panel of human cell lines, revealed TT harmiquine 16 as the most promising compound, as it showed pronounced and selective activity against the tumor cell line HepG2 (IC 50 = 5.48 ± 3.35 μmol L−1). Screening of the antiplasmodial activities of UT harmiquins against erythrocytic stages of the Plasmodium life cycle identified CQ-based UT harmiquine 12 as a novel antiplasmodial hit because it displayed low IC 50 values in the submicromolar range against CQ-sensitive and resistant strains (IC 50 0.06 ± 0.01, and 0.19 ± 0.02 μmol L−1, respectively), and exhibited high selectivity against Plasmodium, compared to mammalian cells (SI = 92).

show abstract

Section: Antiproliferative Activitymentioning

confidence: 97%

mentioning

confidence: 99%

Synthesis, antiproliferative and antiplasmodial evaluation of new chloroquine and mefloquine-based harmiquins

Pavić,

Poje,

Carvalho

et al. 2023

Acta Pharmaceutica

View full text Add to dashboard Cite

show abstract

“…[22] Quinoline and side-chain analogues contribute a centric role in providing huge quinoline-based medications with a significant contribution in the new anti-malarial drug development. [23] Apart from quinolines, [24] other nitrogen, nitrogen/ sulphur/ oxygen containing heterocycles [11] such as indole, [25] phenothiazine, [26] triazoles, [14] β-carboline, [27,28] have also been well explored.…”

Section: Heterocycles As Privileged Scaffold Towards Anti-malarial Ag...mentioning

confidence: 99%

Biannual Account of Anti‐malarial Agents reported in 2021 and 2022: A Comprehensive Coverage

Dhameliya,

Patel,

Kathuria

et al. 2024

ChemistrySelect

View full text Add to dashboard Cite

Malaria remains a severe infectious disease caused by Plasmodium parasites among the primarily afflicting impoverished populations. According to World Health Organization (WHO) report, there were an estimated 247 million malarial cases globally, resulting in approximately 6,19,000 fatalities. Particularly prevalent in tropical and subtropical regions, the development of drug resistance has exacerbated this public health challenge. Consequently, there has been a concrete effort to explore novel compounds with anti‐malarial properties. In continuation of our previous works, this review focuses on heterocyclic compounds documented in 2021 and 2022, including artemisinin, benzimidazole, benzofuran, β‐lactam, coumarin, furan, indole, morpholine, piperazine, pyrimidine, quinoline, triazole, etc. highlighting their efficacy, structural characteristics, in vitro and in vivo activities, among other relevant aspects for the broad interest of medicinal chemists working on the design and development of novel anti‐malarial agents.

show abstract

“…The β-carboline ring is present in many naturally occurring alkaloids with variable biological activities such as anticancer, antimicrobial, anti-Alzheimer, antimalarial, anti-inflammatory, antihypertensive, analgesic, and vasorelaxant activities. − There is a wide interest in the development of novel synthetic approaches, , especially green methods for the preparation of β-carboline derivatives . The green methods used for the synthesis of β-carbolines include the use of microwave , and ultrasonic irradiation, as well as the use of various types of catalysts including heterogeneous, organometallic, , inorganic salts, organic, , natural, , and enzymatic catalysis .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Tetrahydro-β-carboline Derivatives under Electrochemical Conditions in Deep Eutectic Solvents

Mousa,

Adly,

Mahmoud

et al. 2024

ACS Omega

View full text Add to dashboard Cite

In this work, a novel, green, and atom-efficient method for the synthesis of tetrahydro-β-carboline derivatives using electrochemistry (EC) in deep eutectic solvents (DESs) was reported. The EC reaction conditions were optimized to achieve the highest yield. The experimental design was also optimized to perform the reaction in a two-step, one-pot reaction, thereby the time, workup procedure, and solvents needed were all reduced. The new approach achieved our strategy as EC served to decrease the time of reaction, eliminate the use of hazardous catalysts, and lower the energy required for the synthesis of the targeted compounds. On the other side, DESs were used as catalysts, in situ electrolytes, and noninflammable green solvents. The scope of the reaction was investigated using different aromatic aldehydes. Finally, the scalability of the reaction was investigated using a gram-scale reaction that afforded the product in an excellent yield.

show abstract

Current development of β-carboline derived potential antimalarial scaffolds

Cited by 10 publications

References 74 publications

Synthesis, antiproliferative and antiplasmodial evaluation of new chloroquine and mefloquine-based harmiquins

Synthesis, antiproliferative and antiplasmodial evaluation of new chloroquine and mefloquine-based harmiquins

Biannual Account of Anti‐malarial Agents reported in 2021 and 2022: A Comprehensive Coverage

Synthesis of Tetrahydro-β-carboline Derivatives under Electrochemical Conditions in Deep Eutectic Solvents

Contact Info

Product

Resources

About