Targeting DNA Minor Groove by Hybrid Molecules as Anticancer Agents

Nekkanti, Shalini; Tokala, Ramya; Shankaraiah, Nagula

doi:10.2174/0929867324666170523102730

Cited by 53 publications

(34 citation statements)

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“…Furthermore, 1 binds to ds‐DNA/RNA as a groove binder but, in contrast with most groove binders, it also interacts strongly with ss‐RNA, by acting as a spindle around which ss‐RNAs are wrapped due to a combination of electrostatic, H‐bonding and hydrophobic interactions. As most small molecule interactions with ss‐RNA are based on an intercalative binding mode, often combined with additional H‐bonding, whereby helicity of ss‐RNA is preserved or even enhanced, the binding mode of 1 presented herein is unique.…”

Section: Resultsmentioning

confidence: 99%

A Quadrupolar Bis‐Triarylborane Chromophore as a Fluorimetric and Chirooptic Probe for Simultaneous and Selective Sensing of DNA, RNA and Proteins

Ban

Griesbeck

Tomić

et al. 2020

Chemistry A European J

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A water‐soluble tetracationic quadrupolar bis‐triarylborane chromophore showed strong binding to ds‐DNA, ds‐RNA, ss‐RNA, as well as to the naturally most abundant protein, BSA. The novel dye can distinguish between DNA/RNA and BSA by fluorescence emission separated by Δtrueν˜ =3600 cm−1, allowing for the simultaneous quantification of DNA/RNA and protein (BSA) in a mixture. The applicability of such fluorimetric differentiation in vitro was demonstrated, strongly supporting a protein‐like target as a dominant binding site of 1 in cells. Moreover, our dye also bound strongly to ss‐RNA, with the unusual rod‐like structure of the dye, decorated by four positive charges at its termini and having a hydrophobic core, acting as a spindle for wrapping A, C and U ss‐RNAs, but not poly G, the latter preserving its secondary structure. To the best of our knowledge, such unmatched, multifaceted binding activity of a small molecule toward DNA, RNA, and proteins and the selectivity of its fluorimetric and chirooptic response makes the quadrupolar bis‐triarylborane a novel chromophore/fluorophore moiety for biochemical applications.

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Section: Resultsmentioning

confidence: 99%

A Quadrupolar Bis‐Triarylborane Chromophore as a Fluorimetric and Chirooptic Probe for Simultaneous and Selective Sensing of DNA, RNA and Proteins

Ban

Griesbeck

Tomić

et al. 2020

Chemistry A European J

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“…[13,14]. С учетом того, что в качестве узкобороздочных лигандов последние могут оказывать прямое или опосредованное действие на процессы репарации ДНК, проявляя антиканцерогенные эффекты, данные соединения могут быть эффективными в составе препаратов для профилактики рака [44,45].…”

Section: мультифитоадаптоген -жидкий экстрактunclassified

Immunoadhesive regulation using multiphytoadaptogene for spontaneous hepatocarcinomas prevention

Бочаров

Бочарова

Карпова

et al. 2018

Rossijskij bioterapevtičeskij žurnal

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The purposeof this investigation was to evaluate the efficacy of correcting the LFA-1 and Mac-1 leukocyte integrins expression on peripheral blood cells as well as IL-6 and IL-10 serum levels using liquid form multiphytoadaptogene preventive application for hepatocarcinomas incidence suppression and life-span increase of CBA inbreed mice.Materials and methods.The study was carried out on 439 males of inbred CBA mouse strain (subline CBA/LacY). The experimental mice received 10 % liquid form multiphytoadaptogene complex (MPAC) solution in drinking water during the first month of life including the final time period of liver differentiation (preventive administration). MPAC is the standardized herbal formula composed of 40 plant extracts components including adaptogenes Panax ginseng, Eleutherococcus senticosus, Rhodiola rosea, as well as compounds with phenolic structure (flavonoids, triterpene glycosides, etc). Anti-mutagenic, anti-oxidant, immunomodifying activities of MPAC were demonstrated. The CD11a and CD11b antigens expressions on peripheral blood cells were analyzed by indirect immunofluorescence reaction, serum cytokines IL-6 and IL-10 concentrations were determined by enzyme-linked immunosorbent assay as well as the liver tissue morphology were analyzed at the age of 4, 8, 22 months. Tumor incidence and volumes were evaluated at the age of 8 and 22 months. Motor activity and physical status (body weight, coat state) were estimated in the ontogenesis. The average life-span and survival median was analyzed by the Kaplan–Meier method. Statistical analysis was performed with the program STATISTICA 6.0.Results.Inhibited expression of LFA-1 and Mac-1 leukocyte integrins on peripheral blood cells as well as elevated IL-6 and IL-10 serum levels, high incidence of liver tumors (100 % of mice-males), their high number and big sizes in the late period of postnatal ontogenesis in CBA high-cancer inbrede mice, also as life-span not reaching two years was demonstrated. At the same time plural tumor-infiltrating limphocytes were not found. Short-term MPAC preventive administration (during the first month of mouse life occupying the final differentiation period of liver tissue genetically predisposal to hepatoms incidence) revealed the long-term heterotypic adhesion molecules leukocyte integrins LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) up-regulated expression, providing the contact interactions of immune effectors and cancer cells. The events shown is able to enhance the anti-tumor activity of immune reactions including spontaneous hepatocarcinomas lymphocytes infiltration and destruction of tumor tissue. As a result, the hereditary tumors incidence, their number and sizes were reduced as well as life-span and life quality of animals were improved.Conclusion.Up-regulated leukocyte integrins expression on peripheral blood cells, reduced IL-6 and IL-10 serum levels accompanied by tumors lymphocyte infiltration and destruction using MPAC preventive administration is essential for tumor incidence down-regulation. The herbal formula with multiple components is capable to controle anti-tumor immune reactions, as well as the life-span and life quality of high-cancer animals. Hence, the regulation of adhesion violations involved in tumor incidence can be cancer preventive.

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“…Despite the fact that chemotherapeutic agents are currently available, the tolerance, resistance, and unwanted toxic effects toward chemotherapy demand the development of new anticancer agents. DNA, till date, is a major target in cancer therapy owing to its vital role in cell division (replication) and maintenance (transcription), and new chemical entities (NCEs) targeting DNA are remarkable representatives of potent chemotherapeutics . Beyond this, the ability to evade apoptosis stands out as an emerging characteristic of cancer cells, and as a result, compounds inducing apoptosis can evolve into potential anticancer agents.…”

Section: Introductionmentioning

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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Targeting DNA Minor Groove by Hybrid Molecules as Anticancer Agents

Cited by 53 publications

References 0 publications

A Quadrupolar Bis‐Triarylborane Chromophore as a Fluorimetric and Chirooptic Probe for Simultaneous and Selective Sensing of DNA, RNA and Proteins

A Quadrupolar Bis‐Triarylborane Chromophore as a Fluorimetric and Chirooptic Probe for Simultaneous and Selective Sensing of DNA, RNA and Proteins

Immunoadhesive regulation using multiphytoadaptogene for spontaneous hepatocarcinomas prevention

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

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