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In silico studies of piperazine derivatives as potent anti-proliferative agents against PC-3 prostate cancer cell lines.

ABSTRACT: Quantitative Structure Activity Relationship studies were carried out on arylpiperazine derivatives to investigate their anti-proliferate activity against prostate PC-3 cancer cell lines. The built model with statistical parameters; R2 = 0.8483, R2 adj = 0.8078, Q2 cv = 0.7122 and external validation (R2 test) 0.6682 revealed that the anti-proliferate activities were strongly dependent on the descriptors: MATS7c, MATS3e, maxwHBa and WPSA-3. The Variance Inflation Factor of the descriptors were all greater than one but less than two and all descriptors were poorly correlated (r < 0.4). A graph of the experimental activities and predicted activities showed a high correlation and a William's plot showed the presence of only one outlier compound. These results are similar to those reported for stable and robust models with high predicting power. Molecular docking studies of compounds 5 (1-phenyl-4-(4-(2-(p-tolyloxy)ethyl)benzyl)piperazine) and 17 (4-(4-((4-phenylpiperazin-1-yl)methyl)phenethoxy)benzonitrile) with the androgen receptor gave binding affinities of -7.5 and -7.1 kcal/mol respectively. Compound 5 formed a more stable complex having hydrogen, electrostatic and hydrophobic bond interactions while compound 17 had hydrogen and hydrophobic bond interactions only. This study provides a roadmap to the design of more potent anti-prostate cancer compounds.

SUBMITTER: Ikwu FA

PROVIDER: S-EPMC6992985 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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In silico studies of piperazine derivatives as potent anti-proliferative agents against PC-3 prostate cancer cell lines.

Ikwu Fabian A FA Shallangwa Gideon A GA Mamza Paul A PA Uzairu Adamu A

Heliyon 20200123 1

Quantitative Structure Activity Relationship studies were carried out on arylpiperazine derivatives to investigate their anti-proliferate activity against prostate PC-3 cancer cell lines. The built model with statistical parameters; R2 = 0.8483, R2 adj = 0.8078, Q2 cv = 0.7122 and external validation (R2 test) 0.6682 revealed that the anti-proliferate activities were strongly dependent on the descriptors: MATS7c, MATS3e ...[more]

PMID: 32021936

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Project description:The present pathway involves synthesis of isonicotinohydrazide derivatives using isoniazid and diversely substituted aldehydes in the presence of EtOH and catalytic amount of glycerol based carbon sulfonic acid catalyst. The developed pathway has so many merits like excellent yields (91–98%), short reaction time (4–10 min), easy reaction set up, no need of column chromatography, large substrate scope, easily recyclable and reusable catalyst. The synthesized compounds were screened for antimicrobial and anti-tubercular activity and it was observed that compounds possessed high biological potency against the Gram positive and Gram negative bacterial and fungal strains. Regarding anti-tubercular activity, compound 3m exhibited high % inhibition against Mycobacterium tuberculosis H37RV strain. Based on the outcome of in vitro studies, all the synthesized compounds were docked against E. coli (1KZN), C. albicans (1IYL), and M. tuberculosis H37Rv strain (2NSD). The synthesized derivatives were docked within the binding site of 1KZN, and 1IYL. However, with 2NSD, apart from 3h, all the derivatives displayed interaction within the binding cavity of the protein. All the crucial interactions with Asn46, Asp73, and Arg136 in 1KZN, His227, Leu451 in 1IYL, and Tyr158 in 2NSD were witnessed in the top-scored docked candidates. Molecular docking studies revealed the importance of the substitution at R position on isonicotinohydrazide scaffold. The nitrogen atoms of hydrazide moiety were involved in forming hydrogen bonding with the active site amino acids, and the substitution at the R position occupy the hydrophobic position in the binding pocket. Also, the functional groups present on the substituted R position were involved in forming hydrogen bonding with the crucial active site residues. Graphical abstract Synthesis of isonicotinohydrazide analogs and their in vitro and in silico studies.Image 1 Highlights • Isonicotinohydrazide analogs were synthesized in excellent yields (91–98%) in 4–10 min using glycerol based carbon-SO3H catalyst.• The synthesized compounds were screened for anti-microbial activity against bacterial and fungal strains.• The synthesized compounds were examined for anti-tubercular activity.• All the synthesized compounds (3a-o) were docked against 1KZN, 1IYL, and 2NSD proteins.

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In silico studies of piperazine derivatives as potent anti-proliferative agents against PC-3 prostate cancer cell lines.

Publications

In silico studies of piperazine derivatives as potent anti-proliferative agents against PC-3 prostate cancer cell lines.

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