Design, synthesis and cytotoxicity of novel chalcone analogs derived from 1-cyclohexylpyrrolidin-2-one and 2,3-dihydrobenzo[f]chromen-1-one

Kimberly A. Brien, Ravi Kumar Bandi, Ajaya Kumar Behera, Bijay Kumar Mishra, Poulomi Majumdar, Vijay Satam, Mia Savagian, Samuel Tzou, Megan Lee, Matthias Zeller, Andrew J. Robles, Susan L Mooberry, Hari Pati, Moses Lee

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Two divergent series of novel chalcone analogs, one derived from 1-cyclohexylpyrrolidin-2-one and the other derived from 1-benzo[f]chromanone, were designed, synthesized and evaluated for cytotoxicity against two murine cancer cell lines. Two 1-benzo[f]chromanone analogs, 4g and 4j yielded moderate toxicity against both melanoma B16 and lymphoma L1210 cell lines with IC 50 values between the range of 5 and 6μM. With an IC 50 value of 3.4μM, compound 4g was also active against human MDA-MB-435 melanoma cells. X-ray structures of the β-hydroxy ketone product (4a) and the α,β-unsaturated ketone (4h) were collected, and confirm the syn-configuration between the carbonyl moiety and the β-vinylic proton in 4h. X-ray structures of two 1-cyclohexylpyrrolidin-2-one derivatives were also obtained, and both showed an E-configuration for the double bond. Twenty-four chalcone analogs and one aldol product derived from 1-benzo[f]chromanone and N-cyclohexylpyrrolidinone were synthesized and tested for cytotoxicity against murine cancer cells B16 and L1210. One 1-benzo[f]chromanone derivative (4g), containing a 3,4,5-trimethoxy benzylidene moiety, was quite active also against human MDA-MB-435 melanoma cells. The structure and conformation of the target compounds were ascertained by single crystal X-ray analysis of four compounds.

Original languageEnglish (US)
Pages (from-to)341-348
Number of pages8
JournalArchiv der Pharmazie
Volume345
Issue number5
DOIs
StatePublished - May 2012

Fingerprint

Chalcone
X-Rays
Ketones
Melanoma
Cell Line
Experimental Melanomas
Protons
Lymphoma
Neoplasms
2,3-dihydrobenzo(f)chromen-1-one
1-cyclohexylpyrrolidin-2-one

Keywords

  • Benzochromanone
  • Chalcones
  • Cytotoxicity
  • Tubulin
  • X-ray

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmaceutical Science

Cite this

Design, synthesis and cytotoxicity of novel chalcone analogs derived from 1-cyclohexylpyrrolidin-2-one and 2,3-dihydrobenzo[f]chromen-1-one. / Brien, Kimberly A.; Bandi, Ravi Kumar; Behera, Ajaya Kumar; Mishra, Bijay Kumar; Majumdar, Poulomi; Satam, Vijay; Savagian, Mia; Tzou, Samuel; Lee, Megan; Zeller, Matthias; Robles, Andrew J.; Mooberry, Susan L; Pati, Hari; Lee, Moses.

In: Archiv der Pharmazie, Vol. 345, No. 5, 05.2012, p. 341-348.

Research output: Contribution to journalArticle

Brien, KA, Bandi, RK, Behera, AK, Mishra, BK, Majumdar, P, Satam, V, Savagian, M, Tzou, S, Lee, M, Zeller, M, Robles, AJ, Mooberry, SL, Pati, H & Lee, M 2012, 'Design, synthesis and cytotoxicity of novel chalcone analogs derived from 1-cyclohexylpyrrolidin-2-one and 2,3-dihydrobenzo[f]chromen-1-one', Archiv der Pharmazie, vol. 345, no. 5, pp. 341-348. https://doi.org/10.1002/ardp.201100265
Brien, Kimberly A. ; Bandi, Ravi Kumar ; Behera, Ajaya Kumar ; Mishra, Bijay Kumar ; Majumdar, Poulomi ; Satam, Vijay ; Savagian, Mia ; Tzou, Samuel ; Lee, Megan ; Zeller, Matthias ; Robles, Andrew J. ; Mooberry, Susan L ; Pati, Hari ; Lee, Moses. / Design, synthesis and cytotoxicity of novel chalcone analogs derived from 1-cyclohexylpyrrolidin-2-one and 2,3-dihydrobenzo[f]chromen-1-one. In: Archiv der Pharmazie. 2012 ; Vol. 345, No. 5. pp. 341-348.
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abstract = "Two divergent series of novel chalcone analogs, one derived from 1-cyclohexylpyrrolidin-2-one and the other derived from 1-benzo[f]chromanone, were designed, synthesized and evaluated for cytotoxicity against two murine cancer cell lines. Two 1-benzo[f]chromanone analogs, 4g and 4j yielded moderate toxicity against both melanoma B16 and lymphoma L1210 cell lines with IC 50 values between the range of 5 and 6μM. With an IC 50 value of 3.4μM, compound 4g was also active against human MDA-MB-435 melanoma cells. X-ray structures of the β-hydroxy ketone product (4a) and the α,β-unsaturated ketone (4h) were collected, and confirm the syn-configuration between the carbonyl moiety and the β-vinylic proton in 4h. X-ray structures of two 1-cyclohexylpyrrolidin-2-one derivatives were also obtained, and both showed an E-configuration for the double bond. Twenty-four chalcone analogs and one aldol product derived from 1-benzo[f]chromanone and N-cyclohexylpyrrolidinone were synthesized and tested for cytotoxicity against murine cancer cells B16 and L1210. One 1-benzo[f]chromanone derivative (4g), containing a 3,4,5-trimethoxy benzylidene moiety, was quite active also against human MDA-MB-435 melanoma cells. The structure and conformation of the target compounds were ascertained by single crystal X-ray analysis of four compounds.",
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T1 - Design, synthesis and cytotoxicity of novel chalcone analogs derived from 1-cyclohexylpyrrolidin-2-one and 2,3-dihydrobenzo[f]chromen-1-one

AU - Brien, Kimberly A.

AU - Bandi, Ravi Kumar

AU - Behera, Ajaya Kumar

AU - Mishra, Bijay Kumar

AU - Majumdar, Poulomi

AU - Satam, Vijay

AU - Savagian, Mia

AU - Tzou, Samuel

AU - Lee, Megan

AU - Zeller, Matthias

AU - Robles, Andrew J.

AU - Mooberry, Susan L

AU - Pati, Hari

AU - Lee, Moses

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N2 - Two divergent series of novel chalcone analogs, one derived from 1-cyclohexylpyrrolidin-2-one and the other derived from 1-benzo[f]chromanone, were designed, synthesized and evaluated for cytotoxicity against two murine cancer cell lines. Two 1-benzo[f]chromanone analogs, 4g and 4j yielded moderate toxicity against both melanoma B16 and lymphoma L1210 cell lines with IC 50 values between the range of 5 and 6μM. With an IC 50 value of 3.4μM, compound 4g was also active against human MDA-MB-435 melanoma cells. X-ray structures of the β-hydroxy ketone product (4a) and the α,β-unsaturated ketone (4h) were collected, and confirm the syn-configuration between the carbonyl moiety and the β-vinylic proton in 4h. X-ray structures of two 1-cyclohexylpyrrolidin-2-one derivatives were also obtained, and both showed an E-configuration for the double bond. Twenty-four chalcone analogs and one aldol product derived from 1-benzo[f]chromanone and N-cyclohexylpyrrolidinone were synthesized and tested for cytotoxicity against murine cancer cells B16 and L1210. One 1-benzo[f]chromanone derivative (4g), containing a 3,4,5-trimethoxy benzylidene moiety, was quite active also against human MDA-MB-435 melanoma cells. The structure and conformation of the target compounds were ascertained by single crystal X-ray analysis of four compounds.

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