Ergot alkaloids. Synthesis of nitrosourea derivatives of ergolines as potential anticancer agents

Am, Crider; Ck, Lu; Hg, Floss; Jm, Cassady; Ja, Clemens

doi:10.1021/jm00187a008

Cited by 12 publications

(4 citation statements)

References 5 publications

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“…We found 11 drugs with logIC 50 = < −2 μM in at least five cell lines out of 12 (Table ). Of these 11 drugs, six were known anticancer drugs, three were antimicrobial, which have been shown to have an antineoplastic effect, − and two drugs, i.e., viomycin (antimicrobial agent) and diamorphine (analgesic), have yet not been experimentally validated as anticancer drugs. , …”

Section: Resultsmentioning

confidence: 99%

Support Vector Machine-Based Prediction Models for Drug Repurposing and Designing Novel Drugs for Colorectal Cancer

Sengupta,

Singh,

Kumar

2024

ACS Omega

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Colorectal cancer (CRC) has witnessed a concerning increase in incidence and poses a significant therapeutic challenge due to its poor prognosis. There is a pressing demand to identify novel drug therapies to combat CRC. In this study, we addressed this need by utilizing the pharmacological profiles of anticancer drugs from the Genomics of Drug Sensitivity in Cancer (GDSC) database and developed QSAR models using the Support Vector Machine (SVM) algorithm for prediction of alternative and promiscuous anticancer compounds for CRC treatment. Our QSAR models demonstrated their robustness by achieving a high correlation of determination (R 2 ) after 10-fold cross-validation. For 12 CRC cell lines, R 2 ranged from 0.609 to 0.827. The highest performance was achieved for SW1417 and GP5d cell lines with R 2 values of 0.827 and 0.786, respectively. Further, we listed the most common chemical descriptors in the drug profiles of the CRC cell lines and we also further reported the correlation of these descriptors with drug activity. The KRFP314 fingerprint was the predominantly occurring descriptor, with the KRFPC314 fingerprint following closely in prevalence within the drug profiles of the CRC cell lines. Beyond predictive modeling, we also confirmed the applicability of our developed QSAR models via in silico methods by conducting descriptor-drug analyses and recapitulating drug-to-oncogene relationships. We also identified two potential anti-CRC FDA-approved drugs, viomycin and diamorphine, using QSAR models. To ensure the easy accessibility and utility of our research findings, we have incorporated these models into a user-friendly prediction Web server named "ColoRecPred", available at https://project.iith.ac.in/cgntlab/colorecpred. We anticipate that this Web server can be used for screening of chemical libraries to identify potential anti-CRC drugs.

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Section: Resultsmentioning

confidence: 99%

Support Vector Machine-Based Prediction Models for Drug Repurposing and Designing Novel Drugs for Colorectal Cancer

Sengupta,

Singh,

Kumar

2024

ACS Omega

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“…3-Acetamidopiperidine (8). A mixture of 7 (12.2 g, 89.5 mmol), Pt02 (500 mg), and EtOH (175 mL) containing concentrated HCI (7.5 mL) was shaken on the Parr hydrogenator for 42 h. The catalyst was removed by filtration and the solvent was evaporated under reduced pressure to afford an oil.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of nitrosourea derivatives of pyridine and piperidine as potential anticancer agents

Crider¹,

Lamey²,

Floss³

et al. 1980

J. Med. Chem.

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Nitrosourea derivatives 18-22 which utilize either a piperidine or pyridine ring as a carrier group were synthesized and evaluated for anticancer activity. N'-(1-Benzyl-4-piperidinyl)-N-(2-chloroethyl)-N-nitosourea hydrogen maleate (19) exhibited good activity against intracranial L1210 leukemia as well as the mouse ependymoblastoma brain tumor system. Compound 19 exhibited comparable activity in the Lewis lung carcinoma system to N,N'-bis(2-chloroethyl)-N-nitrosourea. Replacement of the N-benzyl group in both the 3-piperidinyl- and 4-piperidinylnitrosoureas resulted in less active compounds in all tumor systems tested. The 3-pyridylnitrosourea 22 was inactive in the L-1210 leukemia system.

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“…Mono-and bis-nitrosourea analogs of 8-amino-6methylergoline, 327 and 328 (Table 18), respectively, were synthesized 287 as examples of compounds which contain both prolactin and anticancer activities. Ergolines are believed 288 to inhibit prolactin release from the anterior pituitary gland by interacting with the prolactin-inhibiting factor (PIF) receptor.…”

Section: Heterocyclic Analogsmentioning

confidence: 99%

“…Ergolines are believed 288 to inhibit prolactin release from the anterior pituitary gland by interacting with the prolactin-inhibiting factor (PIF) receptor. It was hoped 287 that such compounds would target cancers located in the pituitary gland. The two compounds 327 and 328 exhibited 287 moderate in vivo antileukemic activity against the L1210 line (Table 18) but only weak antiprolactin activity, i.e.…”

Section: Heterocyclic Analogsmentioning

confidence: 99%

A Critical Appraisal of the Evolution ofN-Nitrosoureas as Anticancer Drugs

1997

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Ergot alkaloids. Synthesis of nitrosourea derivatives of ergolines as potential anticancer agents

Cited by 12 publications

References 5 publications

Support Vector Machine-Based Prediction Models for Drug Repurposing and Designing Novel Drugs for Colorectal Cancer

Support Vector Machine-Based Prediction Models for Drug Repurposing and Designing Novel Drugs for Colorectal Cancer

Synthesis of nitrosourea derivatives of pyridine and piperidine as potential anticancer agents

A Critical Appraisal of the Evolution ofN-Nitrosoureas as Anticancer Drugs

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