Cytotoxicity and Antineoplastic Activities of Alkylamines and
Their Borane Derivatives

The alkylamines and their related boron derivatives demonstrated potent cytotoxicity against the growth of murine and human tissue cultured cells. These agents did not necessarily require the boron atom to possess potent cytotoxic action in certain tumor lines. Their ability to suppress tumor cell growth was based on their inhibition of DNA and protein syntheses. DNA synthesis was reduced because purine synthesis was blocked at the enzyme site of IMP dehydrogenase by the agents. In addition ribonucleotide reductase and nucleoside kinase activities were reduced by the agents which would account for the reduced d[NTP] pools. The DNA template or molecule may be a target of the drugs with regard to binding of the drug to nucleoside bases or intercalaction of the drug between DNA base pairs. Only some Of the agents caused DNA fragmentation with reduced DNA viscosity. These effects would contribute to overall cell death afforded by the agents.

Download Full-text

New 2-Oxopyridine/2-Thiopyridine Derivatives Tethered to a Benzotriazole with Cytotoxicity on MCF7 Cell Lines and with Antiviral Activities

Letters in Drug Design & Discovery ◽

10.2174/1570180816666190220123547 ◽

2020 ◽

Vol 17 (2) ◽

pp. 124-137 ◽

Cited By ~ 2

Author(s):

Adel Mahmoud Attia ◽

Ahmed Ibrahin Khodair ◽

Eman Abdelnasser Gendy ◽

Mohammed Abu El-Magd ◽

Yaseen Ali Mosa Mohamed Elshaier

Keyword(s):

Dna Damage ◽

Anticancer Agents ◽

Active Compound ◽

Docking Study ◽

Base Pairs ◽

Dna Base ◽

Dna Base Pairs ◽

Antiviral Activities ◽

Active Methylene ◽

Damage Study

Background:Perturbation of nucleic acids structures and confirmation by small molecules through intercalation binding is an intriguing application in anticancer therapy. The planar aromatic moiety of anticancer agents was inserted between DNA base pairs leading to change in the DNA structure and subsequent functional arrest.Objective:The final scaffold of the target compounds was annulated and linked to a benzotriazole ring. These new pharmacophoric features were examined as antiviral and anticancer agents against MCF7 and their effect on DNA damage was also assessed.Methods:A new series of fully substituted 2-oxopyridine/2-thioxopyridine derivatives tethered to a benzotriazole moiety (4a-h) was synthesized through Michael cyclization of synthesized α,β- unsaturated compounds (3a-e) with appropriate active methylene derivatives. The DNA damage study was assessed by comet assay. In silico DNA molecular docking was performed using Open Eye software to corroborate the experimental results and to understand molecule interaction at the atomic level.Results:The highest DNA damage was observed in Doxorubicin, followed by 4h, then, 4b, 4g, 4f, 4e, and 4d. The docking study showed that compound 4h formed Hydrogen Bonds (HBs) as a standard ligand with GSK-3. Compound 4h was the most active compound against rotavirus Wa, HAVHM175, and HSV strains with a reduction of 30%, 40%, and 70%, respectively.Conclusion:Compound 4h was the most active compound and could act as a prospective lead molecule for anticancer agent.

Download Full-text

On the change of the order od stability of DNA base pairs as a result of the methylation of guanine

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19881943 ◽

1988 ◽

Vol 53 (9) ◽

pp. 1943-1945

Author(s):

Pavel Hobza ◽

Camille Sandorfy

Keyword(s):

Ab Initio ◽

Base Pairs ◽

Dispersion Energy ◽

Dna Base ◽

Dna Base Pairs

The interaction of the 6-O methylguanine cation with cytosine and thymine was studied using the ab initio SCF method in combination with a London type expression for dispersion energy. The structure of the complex formed with cytosine differs from that found previously with guanine itself.

Download Full-text

Efficient implementation of the single-reference algebraic diagrammatic construction theory for charged excitations: Applications to the TEMPO radical and DNA base pairs

The Journal of Chemical Physics ◽

10.1063/5.0040317 ◽

2021 ◽

Vol 154 (7) ◽

pp. 074105

Author(s):

Samragni Banerjee ◽

Alexander Yu. Sokolov

Keyword(s):

Efficient Implementation ◽

Base Pairs ◽

Dna Base ◽

Dna Base Pairs ◽

Tempo Radical

Download Full-text

RNA Delivery via DNA-Inspired Janus Base Nanotubes for Extracellular Matrix Penetration

MRS Advances ◽

10.1557/adv.2020.47 ◽

2020 ◽

Vol 5 (16) ◽

pp. 815-823

Author(s):

Ian Sands ◽

Jinhyung Lee ◽

Wuxia Zhang ◽

Yupeng Chen

Keyword(s):

Extracellular Matrix ◽

Small Rnas ◽

Base Pairs ◽

Major Barrier ◽

Dna Base ◽

Dna Base Pairs ◽

Negative Surface ◽

Negative Surface Charge ◽

Delivery Vehicles ◽

Low Cell Density

AbstractRNA delivery into deep tissues with dense extracellular matrix (ECM) has been challenging. For example, cartilage is a major barrier for RNA and drug delivery due to its avascular structure, low cell density and strong negative surface charge. Cartilage ECM is comprised of collagens, proteoglycans, and various other noncollagneous proteins with a spacing of 20nm. Conventional nanoparticles are usually spherical with a diameter larger than 50-60nm (after cargo loading). Therefore, they presented limited success for RNA delivery into cartilage. Here, we developed Janus base nanotubes (JBNTs, self-assembled nanotubes inspired from DNA base pairs) to assemble with small RNAs to form nano-rod delivery vehicles (termed as “Nanopieces”). Nanopieces have a diameter of ∼20nm (smallest delivery vehicles after cargo loading) and a length of ∼100nm. They present a novel breakthrough in ECM penetration due to the reduced size and adjustable characteristics to encourage ECM and intracellular penetration.

Download Full-text