Design, Synthesis and Docking Studies of Flavokawain B Type Chalcones and Their Cytotoxic Effects on MCF-7 and MDA-MB-231 Cell Lines

Design, Synthesis and Docking Studies of Flavokawain B Type Chalcones and Their Cytotoxic Effects on MCF-7 and MDA-MB-231 Cell Lines

Flavokawain B (1) is a natural chalcone extracted from the roots of Piper methysticum, and has been proven to be a potential cytotoxic compound. Using the partial structure of flavokawain B (FKB), about 23 analogs have been synthesized. Among them, compounds 8, 13 and 23 were found in new FKB deriva...

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Main Authors: Addila, Abu Bakar, Akhtar, Muhammad Nadeem, Norlaily, Mohd Ali, Swee, Keong Yeap, Ching, Kheng Quah, Wan-Sin, Loh, Noorjahan Banu, Alitheen, Seema, Zareen, Ul-Haq, Zaheer, Syed Adnan, Ali Shah
Format: Article
Language:English
Published: MDPI - Open Access Publishing 2018
Subjects:
QP Physiology
Online Access:http://umpir.ump.edu.my/id/eprint/20646/
http://umpir.ump.edu.my/id/eprint/20646/
http://umpir.ump.edu.my/id/eprint/20646/
http://umpir.ump.edu.my/id/eprint/20646/7/Design%2C%20Synthesis%20and%20Docking%20Studies%20of%20Flavokawain%20B%20Type-fist-2018.pdf
id ump-20646
recordtype eprints
spelling ump-206462019-10-30T04:13:56Z http://umpir.ump.edu.my/id/eprint/20646/ Design, Synthesis and Docking Studies of Flavokawain B Type Chalcones and Their Cytotoxic Effects on MCF-7 and MDA-MB-231 Cell Lines Addila, Abu Bakar Akhtar, Muhammad Nadeem Norlaily, Mohd Ali Swee, Keong Yeap Ching, Kheng Quah Wan-Sin, Loh Noorjahan Banu, Alitheen Seema, Zareen Ul-Haq, Zaheer Syed Adnan, Ali Shah QP Physiology Flavokawain B (1) is a natural chalcone extracted from the roots of Piper methysticum, and has been proven to be a potential cytotoxic compound. Using the partial structure of flavokawain B (FKB), about 23 analogs have been synthesized. Among them, compounds 8, 13 and 23 were found in new FKB derivatives. All compounds were evaluated for their cytotoxic properties against two breast cancer cell lines, MCF-7 and MDA-MB-231, thus establishing the structure–activity relationship. The FKB derivatives 16 (IC50 = 6.50 ± 0.40 and 4.12 ± 0.20 μg/mL), 15 (IC50 = 5.50 ± 0.35 and 6.50 ± 1.40 μg/mL) and 13 (IC50 = 7.12 ± 0.80 and 4.04 ± 0.30 μg/mL) exhibited potential cytotoxic effects on the MCF-7 and MDA-MB-231 cell lines. However, the methoxy group substituted in position three and four in compound 2 (IC50 = 8.90 ± 0.60 and 6.80 ± 0.35 μg/mL) and 22 (IC50 = 8.80 ± 0.35 and 14.16 ± 1.10 μg/mL) exhibited good cytotoxicity. The lead compound FKB (1) showed potential cytotoxicity (IC50 = 7.70 ± 0.30 and 5.90 ± 0.30 μg/mL) against two proposed breast cancer cell lines. It is evident that the FKB skeleton is unique for anticancer agents, additionally, the presence of halogens (Cl and F) in position 2 and 3 also improved the cytotoxicity in FKB series. These findings could help to improve the future drug discovery process to treat breast cancer. A molecular dynamics study of active compounds revealed stable interactions within the active site of Janus kinase. The structures of all compounds were determined by 1H-NMR, EI-MS, IR and UV and X-ray crystallographic spectroscopy techniques. MDPI - Open Access Publishing 2018 Article PeerReviewed application/pdf en cc_by http://umpir.ump.edu.my/id/eprint/20646/7/Design%2C%20Synthesis%20and%20Docking%20Studies%20of%20Flavokawain%20B%20Type-fist-2018.pdf Addila, Abu Bakar and Akhtar, Muhammad Nadeem and Norlaily, Mohd Ali and Swee, Keong Yeap and Ching, Kheng Quah and Wan-Sin, Loh and Noorjahan Banu, Alitheen and Seema, Zareen and Ul-Haq, Zaheer and Syed Adnan, Ali Shah (2018) Design, Synthesis and Docking Studies of Flavokawain B Type Chalcones and Their Cytotoxic Effects on MCF-7 and MDA-MB-231 Cell Lines. Molecules, 23 (3). pp. 1-14. ISSN 1420-3049 (print); 1420-3049 (online) http://www.mdpi.com/1420-3049/23/3/616 doi:10.3390/molecules23030616
repository_type Digital Repository
institution_category Local University
institution Universiti Malaysia Pahang
building UMP Institutional Repository
collection Online Access
language English
topic QP Physiology
spellingShingle QP Physiology
Addila, Abu Bakar
Akhtar, Muhammad Nadeem
Norlaily, Mohd Ali
Swee, Keong Yeap
Ching, Kheng Quah
Wan-Sin, Loh
Noorjahan Banu, Alitheen
Seema, Zareen
Ul-Haq, Zaheer
Syed Adnan, Ali Shah
Design, Synthesis and Docking Studies of Flavokawain B Type Chalcones and Their Cytotoxic Effects on MCF-7 and MDA-MB-231 Cell Lines
description Flavokawain B (1) is a natural chalcone extracted from the roots of Piper methysticum, and has been proven to be a potential cytotoxic compound. Using the partial structure of flavokawain B (FKB), about 23 analogs have been synthesized. Among them, compounds 8, 13 and 23 were found in new FKB derivatives. All compounds were evaluated for their cytotoxic properties against two breast cancer cell lines, MCF-7 and MDA-MB-231, thus establishing the structure–activity relationship. The FKB derivatives 16 (IC50 = 6.50 ± 0.40 and 4.12 ± 0.20 μg/mL), 15 (IC50 = 5.50 ± 0.35 and 6.50 ± 1.40 μg/mL) and 13 (IC50 = 7.12 ± 0.80 and 4.04 ± 0.30 μg/mL) exhibited potential cytotoxic effects on the MCF-7 and MDA-MB-231 cell lines. However, the methoxy group substituted in position three and four in compound 2 (IC50 = 8.90 ± 0.60 and 6.80 ± 0.35 μg/mL) and 22 (IC50 = 8.80 ± 0.35 and 14.16 ± 1.10 μg/mL) exhibited good cytotoxicity. The lead compound FKB (1) showed potential cytotoxicity (IC50 = 7.70 ± 0.30 and 5.90 ± 0.30 μg/mL) against two proposed breast cancer cell lines. It is evident that the FKB skeleton is unique for anticancer agents, additionally, the presence of halogens (Cl and F) in position 2 and 3 also improved the cytotoxicity in FKB series. These findings could help to improve the future drug discovery process to treat breast cancer. A molecular dynamics study of active compounds revealed stable interactions within the active site of Janus kinase. The structures of all compounds were determined by 1H-NMR, EI-MS, IR and UV and X-ray crystallographic spectroscopy techniques.
format Article
author Addila, Abu Bakar
Akhtar, Muhammad Nadeem
Norlaily, Mohd Ali
Swee, Keong Yeap
Ching, Kheng Quah
Wan-Sin, Loh
Noorjahan Banu, Alitheen
Seema, Zareen
Ul-Haq, Zaheer
Syed Adnan, Ali Shah
author_facet Addila, Abu Bakar
Akhtar, Muhammad Nadeem
Norlaily, Mohd Ali
Swee, Keong Yeap
Ching, Kheng Quah
Wan-Sin, Loh
Noorjahan Banu, Alitheen
Seema, Zareen
Ul-Haq, Zaheer
Syed Adnan, Ali Shah
author_sort Addila, Abu Bakar
title Design, Synthesis and Docking Studies of Flavokawain B Type Chalcones and Their Cytotoxic Effects on MCF-7 and MDA-MB-231 Cell Lines
title_short Design, Synthesis and Docking Studies of Flavokawain B Type Chalcones and Their Cytotoxic Effects on MCF-7 and MDA-MB-231 Cell Lines
title_full Design, Synthesis and Docking Studies of Flavokawain B Type Chalcones and Their Cytotoxic Effects on MCF-7 and MDA-MB-231 Cell Lines
title_fullStr Design, Synthesis and Docking Studies of Flavokawain B Type Chalcones and Their Cytotoxic Effects on MCF-7 and MDA-MB-231 Cell Lines
title_full_unstemmed Design, Synthesis and Docking Studies of Flavokawain B Type Chalcones and Their Cytotoxic Effects on MCF-7 and MDA-MB-231 Cell Lines
title_sort design, synthesis and docking studies of flavokawain b type chalcones and their cytotoxic effects on mcf-7 and mda-mb-231 cell lines
publisher MDPI - Open Access Publishing
publishDate 2018
url http://umpir.ump.edu.my/id/eprint/20646/
http://umpir.ump.edu.my/id/eprint/20646/
http://umpir.ump.edu.my/id/eprint/20646/
http://umpir.ump.edu.my/id/eprint/20646/7/Design%2C%20Synthesis%20and%20Docking%20Studies%20of%20Flavokawain%20B%20Type-fist-2018.pdf
first_indexed 2023-09-18T22:29:54Z
last_indexed 2023-09-18T22:29:54Z
_version_ 1777416215236444160

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