About

Jabeena’s post doctoral research focused on the rational design, synthesis and biological evaluation of libraries of anti-cancer agents.

Publications

7. Design and synthesis of sulphonyl acetamide analogues of quinazoline as anticancer agents

J.Khazir, B.A. Mir, M. Pandita, L. Pilcher, D. Riley and G. Chashoo, Medicinal Chemistry Research, 202029, 916-925.

A series of sulphonyl acetamide analogues were generated on the quinazoline ring through a multistep reaction starting from 2-mercapto-3H-quinazolin-4-one. The library of synthesised analogues was screened for in vitro cytotoxic activity against various human cancer cell lines such as HCT-1 and HT-15 (colon), MCF-7(Breast), PC-3 (Prostrate), SF268 (CNS) using MTT method. From the bioassay results, it was observed that even though most of the synthesised derivatives exhibited a good potency against various screened cancer cell lines, but compound 10d, 10k, and 10n were found to show very potent anticancer activity on all tested cancer cell lines with compound 10d showing IC50 value of 0.08, 0.3 and 0.55 μM on HT-29, MCF-7 and PC-3 cell lines, respectively, compound 10k showing IC50 value of 0.12, 0.03 and 0.08 μM on HCT-15, HT-29 and PC-3 cell lines, respectively, and compound 10n showing IC50 values of 0.1, 0.34, 0.52 and 0.26 on HCT-15, HT-29, MCF-7 and PC-3 cell lines, respectively.

6. Synthesis and anticancer activity of N-9– and N-7- substituted 1,2,3 triazole analogues of 2,6-di-substituted purine

J.Khazir, B.A. Mir, G.Chashoo, L. Pilcher and D. Riley, Medicinal Chemistry Research202029, 33-45.

A library of N-9- and N-7-substituted 1,2,3 triazole analogues were generated on the 2,6-di-substituted purine upon reaction with various substituted aromatic azides. The synthesised analogues were screened for in vitro cytotoxic activity against various human cancer cell lines like (HCT-1 (colon), THP-1 (leukaemia), IMR-32 (neuroblastoma) and A-549 (lung)). From the bioassay results, it was observed that even though most of the synthesized derivatives exhibited a good potency agains various screened cancer cell lines, but few of the analogues like 9a, 9b and 9e were found to be the most potent analogues in the series, with compound 9a showing IC50 values of 0.08 and 0.4 μM against THP-1 and A-549 cell lines, respectively.

5. Design, synthesis and anticancer evaluation of acetamide and hydrazine analogues of pyrimidine

J.Khazir, B.A. Mir, G.Chashoo, T. Maqbool, D. Riley and L.Pilcher, Journal of Heterocyclic Chemistry, 202057, 1306-1318

A library of acetamide and hydrazine analogues were generated on the pyrimidine ring through a multistep reaction starting from 5‐nitro‐pyrimidine‐4,6‐diol and pyrimidine‐4,6‐diol, respectively. The synthesized analogues were screened for in vitro cytotoxic activity against various human cancer cell lines like HCT‐1 and HT‐15 (colon), MCF‐7(breast), PC‐3 (prostrate), SF268 (CNS) using MTT method. From the bioassay results, it was observed that even though many of the synthesized derivatives exhibited a good potency against various screened cancer cell lines, compound 14a from the acetamide series was found to show potent anticancer activity on all the tested cancer cell lines with IC50 value of 0.36μM on CNS cell line and 1.6μM on HT‐21 cell line, and compound 19xxi from hydrazine series of pyrimidine showed potent activity against three tested cancer cell lines with IC50 value of 0.76μM on HT‐29 cell line, 2.6μM on HCT‐15, and 3.2μM on MCF‐7 cell line.

4. Design and synthesis of ring C opened analogues of α-santonin as potential anticancer agents 

J. Khazir, B.A. Mir, L.A. Pilcher, D.L. Riley, G. Chashoo, A. Islam, A.K. Saxena, H.M.S. Kumar,  Medicinal Chemistry Research2016, 25: 2030-2041.

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Here we describe ring opening reaction of a novel halo triene derivative viz., (3S, 5aS)-8-chloro-3a, 4, 5, 5a-tetrahydro-3, 5a, 9-trimethylnaphtho [1, 2-b] furan-2(3H)-one of α-santonin upon nucleophillic attack with alcohols. Halo-triene was synthesized from α-santonin upon reaction with vilsmeier reagent. The synthesized compounds from ring opening reaction were evaluated for anticancer activity against a panel of four human cancer cell lines (A-549, THP-1, HCT-15, and IMR-13). Most of the compounds exhibited promising anticancer activity against all cancer cells in vitro; however compound. 3d with benzyl substitution showed most potent anticancer activity with an IC50 value of 0.3, 0.51, 0.6 and 0.23 μM against A-549, THP-1, HCT-116 and IMR-13 cell lines respectively.

3. Design, synthesis and anticancer activity of Micheal-type thiol adducts of α-santonin analogue with exocyclic methylene

J. Khazir, D.L. Riley, G. Chashoo, B.A. Mir, D. Liles, A. Islam, S.K. Singh, R.A. Vishwakarma, L.A. Pilcher, European Journal of Medicinal Chemistry2015, 101, 769-779.

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A series of Michael-type analogues were generated on the C-ring of α-santonin (α-methylene-γ-butyrolactone) upon reaction with various thiols. All the thiol adducts synthesized were evaluated for their anticancer activity against four human cancer cell lines (PC-3, HCT-15, A-549 and MCF-7). Bioassay results indicated that even though most of the synthesized compounds exhibited a good anticancer activity against various cancer cells in vitro, some of the compounds like 9e9g and 9q were found to be the most promising analogues in this series, with compound 9e showing IC50 values of 1.5 μM, 0.6 μM, 2.4 μM and 1.2 μM on PC-3, MCF-7, A-549 and HCT-116 cell lines respectively. Further, flow cytometry studies showed that MCF-7 cells treated with the compounds 9e, 9g and 9q were arrested in the sub G1 phase of the cell cycle in a concentration dependent manner. These lead molecules were further studied for NF-κB, p65 transcription factor inhibitory activity which confirmed concentration dependent inhibition against NF-κB, p65 with analogue 9e showing 57% inhibition at 2 μM, 9g showing 62% inhibition at 3 μM and 9q showing 54% inhibition at 2 μM concentration.

2. Role of plants in anticancer drug discovery

J. Khazir, B.A. Mir, L. Pilcher, D.L. Riley, Phytochemistry Letters20147, 173-181

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Cancer is one of the major causes of death and the number of new cases, as well as the number of individuals living with cancer, is expanding continuously. Worldwide the alarming rise in mortality rate due to cancer has fuelled the pursuit for effective anticancer agents to combat this disease. Finding novel and efficient compounds of natural origin has been a major point of concern for research in the pharmaceutical sciences. Plants have been seen to possess the potential to be excellent lead structures and to serve as a basis of promising therapeutic agents for cancer treatment. Many successful anti-cancer drugs currently in use or their analogues are plant derived and many more are under clinical trials. This review aims to highlight the invaluable role that plants have played, and continue to play, in the discovery of anticancer agents.

*Phytochemistry Letters Top Cited Author 2014*

1. Anticancer agents from diverse natural sources

 J. Khazir, D.L. Riley, L.A. Pilcher, P. De-Maayer, B.A. Mir, Natural Product Communications2014, 9, 1655-1669.

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This review attempts to portray the discovery and development of anticancer agents/drugs from diverse natural sources. Natural molecules from these natural sources including plants, microbes and marine organisms have been the basis of treatment of human diseases since the ancient times. Compounds derived from nature have been important sources of new drugs and also serve as templates for synthetic modification. Many successful anti-cancer drugs currently in use are naturally derived or their analogues and many more are under clinical trials. This review aims to highlight the invaluable role that natural products have played, and continue to play, in the discovery of anticancer agents.

Conferences

  1. Bi-National Organic Chemistry Conference, Stellenbosch, South Africa, December 2014: Design, Synthesis and Anticancer Activity of α-Santonin Derivatives, Jabeena Khazir,* Lynne A Pilcher, Darren L Riley