DNA-binding affinity and anticancer activity of β-carboline–chalcone conjugates as potential DNA intercalators: Molecular modelling and synthesis

Shankaraiah, Nagula; Siraj, K.P.; Nekkanti, Shalini; Srinivasulu, Vunnam; Sharma, Pankaj; Senwar, Kishna Ram; Sathish, Manda; Vishnuvardhan, M.V.P.S.; Sistla, Ramakrishna; Chetna, Jadala; Nagesh, Narayana; Kamal, Ähmed

doi:10.1016/j.bioorg.2015.02.007

Cited by 91 publications

(33 citation statements)

References 31 publications

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“…Substituted isatins 1 a – c were N‐alkylated by using different alkylating agents in the presence of base followed by subsequent Wolff–Kishner reduction with hydrazine hydrate under reflux conditions to furnish corresponding 2‐oxindoles 3 a ‐ d in good overall yields . Next, other components, 1‐aryl‐9 H ‐pyrido[3,4‐ b ]indole‐3‐carbaldehydes 9 a – g , were synthesized according to reported methods . Commercially available l ‐tryptophan ( 4 ) was esterified by using thionyl chloride in methanol solvent.…”

Section: Resultsmentioning

confidence: 99%

Design and Synthesis of DNA‐Interactive β‐Carboline–Oxindole Hybrids as Cytotoxic and Apoptosis‐Inducing Agents

et al. 2018

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A new series of (E)-3-[(1-aryl-9H-pyrido[3,4-b]indol-3-yl)methylene]indolin-2-one hybrids were synthesized and evaluated for their in vitro cytotoxic activity against a panel of selected human cancer cell lines, namely, HCT-15, HCT-116, A549, NCI-H460, and MCF-7, including HFL. Among the tested compounds, (E)-1-benzyl-5-bromo-3-{[1-(2,5-dimethoxyphenyl)-9H-pyrido[3,4-b]indol-3-yl]methylene}indolin-2-one (10 s) showed potent cytotoxicity against HCT-15 cancer cells with an IC value of 1.43±0.26 μm and a GI value of 0.89±0.06 μm. Notably, induction of apoptosis by 10 s on the HCT-15 cell line was characterized by using different staining techniques, such as acridine orange/ethidium bromide (AO/EB) and DAPI. Further, to understand the mechanism of anticancer effects, various assays such as annexin V-FITC/PI, DCFDA, and JC-1were performed. The flow cytometric analysis revealed that compound 10 s arrests the HCT-15 cancer cells at the G0/G1 phase of the cell cycle. Additionally, western blot analysis indicated that treatment of 10 s on HCT-15 cancer cells led to decreased expression of anti-apoptotic Bcl-2 and increased protein expression of both pro-apoptotic Bax and caspase-3, -8, and -9, and cleaved PARP with reference to actin. Next, a clonogenic assay revealed the inhibition of colony formation in HCT-15 cancer cells by 10 s in a dose-dependent manner. Moreover, upon testing on normal human lung cells (HFL), the compounds were observed to be safer with a low toxicity profile. In addition, viscosity and molecular-docking studies showed that compound 10 s has typical intercalation with DNA.

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Section: Resultsmentioning

confidence: 99%

Design and Synthesis of DNA‐Interactive β‐Carboline–Oxindole Hybrids as Cytotoxic and Apoptosis‐Inducing Agents

et al. 2018

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“…[42] We predicted that water played ak ey role in the allylation reaction, as well as in the subsequent lactonization process,f or the diastereoselectives ynthesis of thesec onjugates. Dual activation was performed by water,b yi ncreasing the electrophilic character of the formyl and ester functionalities and simultaneously boosting the nucleophilicity of the hydroxy group to expedite the in situ intramolecularl actonization of the homoallyl alcohol (64).…”

Section: Synthesis Of C1-tethered B-carboline Frameworkmentioning

confidence: 99%

“…The DNA intercalation of these b-carbo-lineÀchalcone conjugates (170)w as also investigated. [64] Kamal and co-workers developeda nother series of new C3linked b-carbolineÀpyridine derivatives (171)t hrough am odified-Khronke reactionb ye xploring C3-linked b-carbolineÀchalcones (170;S cheme62). [65] The DNA-binding affinitieso ft hese derivativesw ere investigated and significant enhancement was observed( DT m = 6.3 and 6.5 8Ca fter 0a nd 18 hi ncubation) compared to the standard Doxorubicin (DT m = 2.4 and 2.6 8C, respectively).…”

Section: Synthesis and Application Of 3-formyl-9h-b-carbolinesmentioning

confidence: 99%

1(3)‐Formyl‐β‐carbolines: Potential Aldo‐X Precursors for the Synthesis of β‐Carboline‐Based Molecular Architectures

et al. 2017

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b-Carboline, ap rivileged scaffold in the alkaloid family,h as ab road spectrum of medicinal properties and is found in severalc ommercial drugs, such as tadalafil, cipargamin, anda becarnil. Owing to the immense pharmacological importance of b-carboline derivatives, their synthesis has been one of the frontier areas of research in recent years. In this context,1 (3)-formyl-9H-b-carbolines are promising "aldo-X" bifunctional building blocks (AXB3s) that offer alternate avenues for the diversity-oriented synthesis of b-carboline derivatives. This Focus Review is an assimilation of recent literature (2011)(2012)(2013)(2014)(2015)(2016)(2017) pertaining to the synthesis and applicationso f1 (3)-formyl-b-carbolines for the construction of b-carboline-tethered and -fused moleculara rchitectures. In addition, the medicinal potential of b-carboline derivatives has been highlighted.

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“…The formation of these nucleuses is mainly constituted with the reaction of unsaturated carbonyl unit of chalcone (Singh and Bhati, 2011). Chalcone is a unique template that is associated with several promising biological activities such as antimicrobial (Ahmed et al, 2015), antiinflammatory (Sashidhara et al, 2011), antimalarial (Pingaew et al, 2014), anticancer (Görgülü et al, 2015;Shankaraiah et al, 2015), antileishmanial (Boeck et al, 2006), and antimalarial (Tadigoppula et al, 2013). Moreover, chalcones find several applications in agriculture; for example, insect antifeedant (Thirunarayanan andVanangamudi, 2014, Kumar et al, 2012) and larvicidal (Pasquale et al, 2012;Satyavani et al, 2015) activities have also been shown by chalcone derivatives.…”

Section: Introductionmentioning

confidence: 99%

Discovery and structure activity relationships of 2-pyrazolines derived from chalcones from a pest management perspective

Koçyığıt‐Kaymakcioğlu

Beyhan

Tabanca

et al. 2015

Med Chem Res

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Synthesis of chalcones and 2-pyrazoline derivatives has been an active field of research due to the established pharmacological effects of these compounds. In this study, a series of chalcone (1a-i), 2-pyrazoline-1-carbothioamides (2a-i), and 2-pyrazoline-1-carboxamide derivatives (3a-g) were synthesized and screened for their potential pesticide activities. The proposed structures of all the synthesized compounds were confirmed using the elemental analysis, UV, IR, 1 H-NMR, and mass spectroscopy. Among the total of 25 tested compounds, compounds 1g and 2a and 2e with Biting Deterrence Index (BDI) values of 0.85, 0.83, and 0.8, respectively, at 25 nmol/cm 2 showed the highest biting deterrent activity against Aedes aegypti, which was comparable to N,N-diethyl-3-methylbenzamide (DEET). Compounds 1g, 2a and 2e were subsequently tested in human-based repellent bioassays, and they showed MED (minimum effective dose) values of 0.375, 0.094, and 0.375 mg/cm 2 , respectively. Compound 1e was the most toxic compound (LC 50 = 2.58 ppm), followed by 1f (LC 50 = 5.69 ppm) and 2g (LC 50 = 15.14 ppm), against 1-day-old Ae. aegypti larvae. Compounds 1f and 2h 1f and 2h showed the greatest growth inhibition against Colletotrichum gloeosporioides (97.6 and 98.5 %, respectively) at the lowest dose (0.3 lM), which was greater antifungal activity than with standard commercial fungicides captan and azoxystrobin. Compounds 2d, 2g and 2h produced 79.5, 98.3, and 82.3 % growth inhibition, respectively, at 30.0 lM against Botrytis cinerea, which was similar to captan in the antifungal activity. The active fungicidal compounds (2d, 2g, and 2h) were weaky phytotoxic, with little or no phytotoxicity at concentrations that were fungitoxic. Compound 2h stimulated the growth of Lemma paucicostata at concentrations that are fungitoxic to several plant pathogens.

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DNA-binding affinity and anticancer activity of β-carboline–chalcone conjugates as potential DNA intercalators: Molecular modelling and synthesis

Cited by 91 publications

References 31 publications

Design and Synthesis of DNA‐Interactive β‐Carboline–Oxindole Hybrids as Cytotoxic and Apoptosis‐Inducing Agents

Design and Synthesis of DNA‐Interactive β‐Carboline–Oxindole Hybrids as Cytotoxic and Apoptosis‐Inducing Agents

1(3)‐Formyl‐β‐carbolines: Potential Aldo‐X Precursors for the Synthesis of β‐Carboline‐Based Molecular Architectures

Discovery and structure activity relationships of 2-pyrazolines derived from chalcones from a pest management perspective

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