Anti-proliferative and anti-malarial activities of spiroisoxazoline analogues of artemisinin

Surya Pratap; Fatima Naaz; Srinivas Reddy; Kunal K. Jha; Kalicharan Sharma; Dinakar Sahal; Mymoona Akhter; Devanna Nayakanti; Halmuthur M.S. Kumar; Vandana; Kailash Pandey; Syed Shafi

doi:10.1002/ardp.201800192

Anti-proliferative and anti-malarial activities of spiroisoxazoline analogues of artemisinin

Surya Pratap
, Fatima Naaz
, Srinivas Reddy
, Kunal K. Jha
, Kalicharan Sharma
, Dinakar Sahal
, Mymoona Akhter
, Devanna Nayakanti
, Halmuthur M.S. Kumar
, Vandana
, Kailash Pandey
, Syed Shafi

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

A series of spiroisoxazoline analogues of artemisinin was synthesized by employing 1,3-dipolar cycloaddition between various in situ generated nitrile oxides and artemisitene. All the synthesized compounds were tested for their anti-proliferative and anti-malarial activities. Among the compounds tested, compound 11a was found to be potent against the HCT-15 cancer cell line with IC ₅₀ = 4.04 μM when compared to 5-fluorouracil (IC ₅₀ = 35.53 μM). DNA cell cycle analysis shows that 11a was inhibiting cell proliferation at the G2/M phase. Compound 11b was found to be most active against Plasmodium falciparum with IC ₅₀ = 0.1 μM and also blocked host hemoglobin hydrolysis by the falcipain-3 receptor. It was demonstrated to have better dynamics of parasite killing efficiency than artemisinin. Molecular docking studies revealed that these compounds interacted with falcipain-3 receptor sites.

Original language	English (US)
Article number	1800192
Journal	Archiv der Pharmazie
Volume	352
Issue number	1
DOIs	https://doi.org/10.1002/ardp.201800192
State	Published - Jan 2019
Externally published	Yes

Keywords

1,3-dipolar cycloaddition
anti-malarial activity
anti-proliferative
artemisitene
spiroisoxazoline

ASJC Scopus subject areas

Pharmaceutical Science
Drug Discovery

Access to Document

10.1002/ardp.201800192

Cite this

@article{df2c518714af49728ea3e4929fc1fd8e,

title = "Anti-proliferative and anti-malarial activities of spiroisoxazoline analogues of artemisinin",

abstract = " A series of spiroisoxazoline analogues of artemisinin was synthesized by employing 1,3-dipolar cycloaddition between various in situ generated nitrile oxides and artemisitene. All the synthesized compounds were tested for their anti-proliferative and anti-malarial activities. Among the compounds tested, compound 11a was found to be potent against the HCT-15 cancer cell line with IC 50 = 4.04 μM when compared to 5-fluorouracil (IC 50 = 35.53 μM). DNA cell cycle analysis shows that 11a was inhibiting cell proliferation at the G2/M phase. Compound 11b was found to be most active against Plasmodium falciparum with IC 50 = 0.1 μM and also blocked host hemoglobin hydrolysis by the falcipain-3 receptor. It was demonstrated to have better dynamics of parasite killing efficiency than artemisinin. Molecular docking studies revealed that these compounds interacted with falcipain-3 receptor sites.",

keywords = "1,3-dipolar cycloaddition, anti-malarial activity, anti-proliferative, artemisitene, spiroisoxazoline",

author = "Surya Pratap and Fatima Naaz and Srinivas Reddy and Jha, \{Kunal K.\} and Kalicharan Sharma and Dinakar Sahal and Mymoona Akhter and Devanna Nayakanti and Kumar, \{Halmuthur M.S.\} and Vandana and Kailash Pandey and Syed Shafi",

note = "Publisher Copyright: {\textcopyright} 2018 Deutsche Pharmazeutische Gesellschaft",

year = "2019",

month = jan,

doi = "10.1002/ardp.201800192",

language = "English (US)",

volume = "352",

journal = "Archiv der Pharmazie",

issn = "0365-6233",

publisher = "Wiley-VCH Verlag",

number = "1",

}

TY - JOUR

T1 - Anti-proliferative and anti-malarial activities of spiroisoxazoline analogues of artemisinin

AU - Pratap, Surya

AU - Naaz, Fatima

AU - Reddy, Srinivas

AU - Jha, Kunal K.

AU - Sharma, Kalicharan

AU - Sahal, Dinakar

AU - Akhter, Mymoona

AU - Nayakanti, Devanna

AU - Kumar, Halmuthur M.S.

AU - Vandana,

AU - Pandey, Kailash

AU - Shafi, Syed

PY - 2019/1

Y1 - 2019/1

N2 - A series of spiroisoxazoline analogues of artemisinin was synthesized by employing 1,3-dipolar cycloaddition between various in situ generated nitrile oxides and artemisitene. All the synthesized compounds were tested for their anti-proliferative and anti-malarial activities. Among the compounds tested, compound 11a was found to be potent against the HCT-15 cancer cell line with IC 50 = 4.04 μM when compared to 5-fluorouracil (IC 50 = 35.53 μM). DNA cell cycle analysis shows that 11a was inhibiting cell proliferation at the G2/M phase. Compound 11b was found to be most active against Plasmodium falciparum with IC 50 = 0.1 μM and also blocked host hemoglobin hydrolysis by the falcipain-3 receptor. It was demonstrated to have better dynamics of parasite killing efficiency than artemisinin. Molecular docking studies revealed that these compounds interacted with falcipain-3 receptor sites.

AB - A series of spiroisoxazoline analogues of artemisinin was synthesized by employing 1,3-dipolar cycloaddition between various in situ generated nitrile oxides and artemisitene. All the synthesized compounds were tested for their anti-proliferative and anti-malarial activities. Among the compounds tested, compound 11a was found to be potent against the HCT-15 cancer cell line with IC 50 = 4.04 μM when compared to 5-fluorouracil (IC 50 = 35.53 μM). DNA cell cycle analysis shows that 11a was inhibiting cell proliferation at the G2/M phase. Compound 11b was found to be most active against Plasmodium falciparum with IC 50 = 0.1 μM and also blocked host hemoglobin hydrolysis by the falcipain-3 receptor. It was demonstrated to have better dynamics of parasite killing efficiency than artemisinin. Molecular docking studies revealed that these compounds interacted with falcipain-3 receptor sites.

KW - 1,3-dipolar cycloaddition

KW - anti-malarial activity

KW - anti-proliferative

KW - artemisitene

KW - spiroisoxazoline

UR - https://www.scopus.com/pages/publications/85058185350

UR - https://www.scopus.com/pages/publications/85058185350#tab=citedBy

U2 - 10.1002/ardp.201800192

DO - 10.1002/ardp.201800192

M3 - Article

C2 - 30537298

AN - SCOPUS:85058185350

SN - 0365-6233

VL - 352

JO - Archiv der Pharmazie

JF - Archiv der Pharmazie

IS - 1

M1 - 1800192

ER -

Anti-proliferative and anti-malarial activities of spiroisoxazoline analogues of artemisinin

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this