Design, synthesis and molecular docking of piperidin‐4‐amine linked pyrimidine derivatives as potent anticancer agents

Gangireddy, Madhu Sudhana Reddy; Mantipally, Manohar; Badavath, Vishnu Nayak; Maddipati, Venkatanarayana Chowdary; Paidikondala, Kalyani; Katari, Naresh Kumar; Gundla, Rambabu

doi:10.1016/j.cdc.2021.100646

Cited by 6 publications

(2 citation statements)

References 31 publications

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“…The synthesized compounds (8a-8l) were evaluated for their in-vitro cytotoxicity against various cancer cell lines such as DU145 (prostate cancer), SKOV3 (ovarian carcinoma), MCF-7 (breast cancer) cell lines, HeLa (cervix) cell lines, along with AD293 (non-cancerous cellline) by MTT assay using a reported protocol [9][10][11][12]. All the compounds were found to be cytotoxic to cancerous cell lines when compared with Tubastatin A (Table 1).…”

Section: Anti-proliferative (Mtt) Assaymentioning

confidence: 99%

Design, and synthesis of N‐benzyl spiro‐piperidine hydroxamic acid‐based derivatives: Histone deacetylase inhibitory activity and drug‐likeness prediction

Kurapati

Paidikondala²,

Badavath

et al. 2022

Journal of Heterocyclic Chem

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Nonselective histone deacetylase (HDAC) inhibitors show dose-limiting side effects due to the inhibition of multiple, essential HDAC subtypes that can be limited by selective inhibitors. We herein synthesized a new series of N-benzyl spiropiperidinehydroxamic acid-based derivatives, which have been identified as a zincbinding group by combining privileged structures with hydroxamic acid and N-benzyl spiro-piperidine. All the synthesized compounds had good antiproliferative activity against various tumor cell lines and were non-toxic to the normal cells, AD293. Compound with halogen substitution (8i: 2,4-dichloro and 8k: 2,4-difluoro) shown 101.5-and 108-fold selectivity towars HDAC6 inhibition over HDAC8 in-vitro fluorometric-based assay and compared with Tubastatin A. The obtained in-vitro results were in agreement with molecular docking studies. The identified novel compounds occupy the catalytic domain of HDAC6 selectively and shed light on the role of both chlorine and fluorine instead of fluorination on benzohydroxamate-based (ACS Med. Chem. Lett. 2021, 12(11), 1810-1817) structure over class I isoforms. These obtained results can be used in the design of novel, highly selective HDAC6 inhibitors.

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Section: Anti-proliferative (Mtt) Assaymentioning

confidence: 99%

Design, and synthesis of N‐benzyl spiro‐piperidine hydroxamic acid‐based derivatives: Histone deacetylase inhibitory activity and drug‐likeness prediction

Kurapati

Paidikondala²,

Badavath

et al. 2022

Journal of Heterocyclic Chem

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“…Substituted piperidin-4-amine derivatives exhibited as antifungal, antihistaminic, antimicrobial [12,13], antitubercular, anthelmintic, antipsychotic agents [13] as these derivatives are versatile ring systems and well established medicinally useful class of compounds. Piperidin-4-amine derivatives are used as cognition enhancing drugs [14] and anticancer medicines include pyrimidine derivatives with piperidin-4-amine linkage [15]. Ruthenium(III) is a well-known catalyst for redox reactions in alkaline environments [16,17].…”

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confidence: 99%

A Spectroscopic Approach on Permanganate Oxidation of 1-[(4-Chlorophenyl)methyl]piperidin-4-amine in Presence of Ruthenium(III) Catalyst with DFT Analysis on Reaction Mechanism Pathway

Shashidhar,

Shastry,

Chinnam

et al. 2023

ajc

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The kinetic oxidation of 1-[(4-chlorophenyl)methyl]piperidin-4-amine (CMP) using alkaline potassium permanganate in presence of Ru(III) as catalyst was conducted spectrophotometrically at 303 K. The Pseudo first-order reaction was maintained with regard to oxidant and substrate during the reaction at an ionic strength of 0.01 mol dm-3. The first-order kinetics has been depicted with respect to catalyst Ru(III) chloride and less than unit order with substrate and medium. For the slow step, different activation parameters including ΔH# (kJ mol-1), Ea (kJ mol-1), ΔG# (kJ mol-1) and ΔS# (J K-1 mol-1) were calculated. The effect of temperature, variation of substrate concentration, oxidant, ionic strength were studied. The stoichiometry ratio of the reaction to the substrate and oxidizing agent was found to be 1:4. The products of reaction were isolated and identified as chlorobenzene and L-alanine, N-(2-aminomethylethyl)-carboxylic acid by LC-MS spectra, a suitable mechanism has been proposed and the rate laws are derived. The frontier molecular orbital (FMO) and frontier electron density (FED) of piperidiamine and the oxidative products were studied using density functional theory (DFT). The results of the theoretical calculations supported the suggested reaction pathways.

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A comprehensive review on pyrimidine analogs-versatile scaffold with medicinal and biological potential

Basha¹,

Goudgaon

2021

Journal of Molecular Structure

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Design, synthesis and molecular docking of piperidin‐4‐amine linked pyrimidine derivatives as potent anticancer agents

Cited by 6 publications

References 31 publications

Design, and synthesis of N‐benzyl spiro‐piperidine hydroxamic acid‐based derivatives: Histone deacetylase inhibitory activity and drug‐likeness prediction

Design, and synthesis of N‐benzyl spiro‐piperidine hydroxamic acid‐based derivatives: Histone deacetylase inhibitory activity and drug‐likeness prediction

A Spectroscopic Approach on Permanganate Oxidation of 1-[(4-Chlorophenyl)methyl]piperidin-4-amine in Presence of Ruthenium(III) Catalyst with DFT Analysis on Reaction Mechanism Pathway

A comprehensive review on pyrimidine analogs-versatile scaffold with medicinal and biological potential

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