Kavita Shah

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Name: Shah, Kavita

Organization: Purdue University , USA

Department: Department of Chemistry and Purdue Cancer Center

Title: (PhD)

Chemicals
References

A Tale of the Good and Bad: Remodeling of the Microtubule Network in the Brain by Cdk5

Co-reporter:Kavita Shah;Debomoy K. Lahiri

Molecular Neurobiology 2017 Volume 54( Issue 3) pp:2255-2268

Publication Date(Web):05 March 2016

DOI:10.1007/s12035-016-9792-7

Cdk5, a cyclin-dependent kinase family member, is a global orchestrator of neuronal cytoskeletal dynamics. During embryogenesis, Cdk5 is indispensable for brain development. In adults, it is essential for numerous neuronal processes, including higher cognitive functions such as learning and memory formation, drug addiction, pain signaling, and long-term behavior changes through long-term potentiation and long-term depression, all of which rely on rapid alterations in the cytoskeleton. Cdk5 activity becomes deregulated in various brain disorders, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, attention-deficit hyperactivity disorder, epilepsy, schizophrenia, and ischemic stroke; these all result in profound remodeling of the neuronal cytoskeleton. This Commentary specifically focuses on the pleiotropic contribution of Cdk5 in regulating neuronal microtubule remodeling. Because the vast majority of the physiological substrates of Cdk5 are associated with the neuronal cytoskeleton, our emphasis is on the Cdk5 substrates, such as CRMP2, stathmin, drebrin, dixdc1, axin, MAP2, MAP1B, doublecortin, kinesin-5, and tau, that have allowed to unravel the molecular mechanisms through which Cdk5 exerts its divergent roles in regulating neuronal microtubule dynamics, both in healthy and disease states.

Synthesis and anticancer activity study of indolyl hydrazide–hydrazones

Co-reporter:Swapna Sundaree;Buchi Reddy Vaddula;Mukund P. Tantak

Medicinal Chemistry Research 2016 Volume 25( Issue 5) pp:941-950

Publication Date(Web):2016 May

DOI:10.1007/s00044-016-1522-1

A series of N′-((1-(substituted)-1H-indol-3-yl)methylene)hydrazides were synthesized and evaluated for their in vitro antiproliferative activities against various cancer cell lines. Formation of indole hydrazide–hydrazones was accomplished by the reaction of indole 3-carboxaldehyde with aryl/alkyl hydrazides in the presence of acetic acid. Out of synthesized twenty-two compounds, some of the analogs exhibited specificity toward breast (18b, 18d, 18f and 18j) and prostate (18t and 18v) cancer cells. Among the prepared derivatives, compounds 18b, 18d and 18j were most cytotoxic (IC50 = 0.9, 0.4 and 0.8 µM, respectively) against the screened cancer cell lines. Exposure of PC3 cells to either 18d or 18j resulted in increased levels of cleaved PARP1, indicating that indolyl hydrazide–hydrazones induce apoptosis in PC3 cells.

Sequential one-pot synthesis of bis(indolyl)glyoxylamides: Evaluation of antibacterial and anticancer activities

Co-reporter:Mukund P. Tantak, Vishakha Gupta, Kumar Nikhil, V. Arun, Rajnish Prakash Singh, Prabhat Nath Jha, Kavita Shah, Dalip Kumar

Bioorganic & Medicinal Chemistry Letters 2016 26(13) pp: 3167-3171

Publication Date(Web):1 July 2016

DOI:10.1016/j.bmcl.2016.04.080

A series of bis(indolyl)glyoxylamides 10a–n has been designed and synthesized. In situ generated indole-3-glyoxalylchloride from the reaction of readily available indole 9 with oxalyl chloride was treated with tryptamine to produce bis(indolyl)glyoxylamides 10a–n in 82–93% yields. All the synthesized bis(indolyl)glyoxylamides were well characterized and tested for their antibacterial activity against Gram-positive and Gram-negative bacterial strains. Compounds 10d, 10g and 10i were found to display potent antibacterial activity against Gram-negative strain. Further, the cytotoxicity of bis(indolyl)glyoxylamides 10a–n were evaluated against a panel of human cancer cell lines. Of the screened analogues, compound 10f (IC50 = 22.34 μM; HeLa, 24.05 μM; PC-3, 21.13 μM; MDA-MB-231 and 29.94 μM; BxPC-3) was identified as the most potent analogue of the series. Exposure of PC-3 cells to either 10a or 10f resulted in increased levels of cleaved PARP1, indicating that bis(indolyl)glyoxylamides induce apoptosis in PC-3 cells. Most importantly, compounds 10d, 10g and 10i were completely ineffective in mammalian cells, suggesting that they target bacterial-specific targets and thus will not display any toxicity in host cells.Download high-res image (139KB)Download full-size image

Synthesis and Biological Evaluation of 2-Arylamino-5- (3-Indolyl)-1,3,4-Oxadiazoles as Potent Cytotoxic Agents

Co-reporter:Mukund P Tantak;Anil Kumar;Brett Noel; Kavita Shah; Dalip Kumar

ChemMedChem 2013 Volume 8( Issue 9) pp:1468-1474

Publication Date(Web):

DOI:10.1002/cmdc.201300221

A series of 2-arylamino-5-(indolyl)-1,3,4-thiadiazoles as potent cytotoxic agents

Co-reporter:Dalip Kumar, N. Maruthi Kumar, Brett Noel, Kavita Shah

European Journal of Medicinal Chemistry 2012 Volume 55() pp:432-438

Publication Date(Web):September 2012

DOI:10.1016/j.ejmech.2012.06.047

A series of 2-arylamino-5-(indolyl)-1,3,4-thiadiazoles 6a–v were prepared and studied for their anticancer activity against selected human cancer cell lines. The reaction of indolylhydrazides 3a–h with a variety of aryl isothiocyanates 4 afforded the key intermediate thiosemicarbazides 5a–v, which upon treatment with acetyl chloride produced the 2-arylamino-5-(indolyl)-1,3,4-thiadiazoles 6a–v in good yields. Most of the synthesized compounds showed selective cytotoxicity towards human breast cancer cell line (MDA-MB-231). Of the synthesized 2-arylamino-5-(indolyl)-1,3,4-thiadiazoles, compound 6f is the most potent towards tested cancer cell lines (IC50 = 0.15–1.18 μM).Graphical abstractHighlights► Diverse series of novel 2-arylamino-5-(indolyl)-1,3,4-thiadiazoles were synthesized. ► All the compounds were evaluated for their in-vitro anticancer activity. ► The compounds are selective against MDA-MB-231 cancer cell line (IC50 < 1 μM). ► The most potent compound showed IC50 value of 150 nM against LnCap cancer cell line.

Novel bis(indolyl)hydrazide–hydrazones as potent cytotoxic agents

Co-reporter:Dalip Kumar, N. Maruthi Kumar, Soumitra Ghosh, Kavita Shah

Bioorganic & Medicinal Chemistry Letters 2012 Volume 22(Issue 1) pp:212-215

Publication Date(Web):1 January 2012

DOI:10.1016/j.bmcl.2011.11.031

A series of bis(indolyl) hydrazide–hydrazones 5a–n were synthesized and evaluated for their cytotoxicity against selected human cancer cell lines. The reaction of indole-3-carboxaldehyde 2 with indole-3-carbohydrazide 4 in presence of catalytic amount of acetic acid afforded 5a–n in good yields. Among the synthesized bis(indolyl)hydrazide–hydrazones, the compound 5b with N-(p-chlorobenzyl) and bromo substituents was found to be the most potent against multiple cancer cell lines (IC50 = 1.0 μM, MDA-MB-231). The compound 5k exhibited selective cytotoxicity against breast cancer cell line MCF7 (IC50 = 3.1 μM).

A Facile Synthesis of Novel Bis-(indolyl)-1,3,4-oxadiazoles as Potent Cytotoxic Agents

Co-reporter: Dalip Kumar;V. Arun;N. MaruthiKumar;Glen Acosta;Brett Noel; Kavita Shah

ChemMedChem 2012 Volume 7( Issue 11) pp:1915-1920

Publication Date(Web):

DOI:10.1002/cmdc.201200363

Synthesis of novel 1,2,4-oxadiazoles and analogues as potential anticancer agents

Co-reporter:Dalip Kumar, Gautam Patel, Angela K. Chavers, Kuei-Hua Chang, Kavita Shah

European Journal of Medicinal Chemistry 2011 Volume 46(Issue 7) pp:3085-3092

Publication Date(Web):July 2011

DOI:10.1016/j.ejmech.2011.03.031

A library of 3,5-disubstituted-1,2,4-oxadiazoles 7–9 and their bioisosters, 1,3,4-oxadiazole 14 and 1,3,4-thiadiazole 16, were synthesized and evaluated in vitro for their anticancer potential against a panel of six human cancer cell lines. The key step in the synthesis of oxadiazoles 7–9 involve coupling of amidoxime 6 with an appropriate carboxylic acid followed by thermal cyclization. The bioisosteres, 1,3,4-oxadiazole 14 and 1,3,4-thiadiazole 16 were prepared from the reaction of a common precursor diacylhydrazine 13 with thionyl chloride and Lawesson′s reagent, respectively. The anticancer studies on the synthesized compounds revealed that presence of a cyclopentyloxy or n-butyloxy on the C-3 aryl ring and piperdin-4-yl or trichloromethyl at the C-5 position of 1,2,4-oxadiazole is essential for good activity. In particular, 1,2,4-oxadiazole 7i and analogue 1,3,4-thiadiazole 16 exhibited significant activity against DU145 (IC50: 9.3 μM) and MDA-MB-231 (IC50: 9.2 μM) cell lines, respectively.A new series of 1,2,4-oxadiazoles were synthesized and evaluated in vitro for their anticancer activity against various human cancer cell lines.Highlights► Novel 3,5-disubstituted-1,2,4-oxadiazoles and their analogues were synthesized. ► The 1,2,4-oxadiazole 7i exhibited promising cytotoxicity against DU145 cell line. ► The 1,3,4-thiadiazole 16 exhibited promising cytotoxicity against MDA-MB-231 cell line.

Glutathione-S-transferase P1 is a critical regulator of Cdk5 kinase activity

Co-reporter:Kai-Hui Sun;Kuei-Hua Chang;Sara Clawson;Soumitra Ghosh;Hamid Mirzaei;Fred Regnier

Journal of Neurochemistry 2011 Volume 118( Issue 5) pp:902-914

Publication Date(Web):

DOI:10.1111/j.1471-4159.2011.07343.x

J. Neurochem. (2011) 118, 902–914.

Abstract

Cyclin dependent kinase-5 (Cdk5) activity is deregulated in Alzheimer’s disease (AD) and contributes to all three hallmarks: neurotoxic β-amyloid formation, neurofibrillary tangles, and neuronal death. However, the mechanism leading to Cdk5 deregulation remains controversial. Cdk5 deregulation in AD is usually linked to the formation of p25, a proteolysis product of Cdk5 activator p35, which leads to Cdk5 mislocalization and hyperactivation. A few studies have indeed shown increased p25 levels in AD brains; however, others have refuted this observation. These contradictory findings suggest that additional factors contribute to Cdk5 deregulation. This study identified glutathione-S-transferase pi 1 (GSTP1) as a novel Cdk5 regulatory protein. We demonstrate that it is a critical determinant of Cdk5 activity in human AD brains and various cancer and neuronal cells. Increased GSTP1 levels were consistently associated with reduced Cdk5 activity. GSTP1 directly inhibits Cdk5 by dislodging p25/p35, and indirectly by eliminating oxidative stress. Cdk5 promotes and is activated by oxidative stress, thereby engaging a feedback loop which ultimately leads to cell death. Not surprisingly, GSTP1 transduction conferred a high degree of neuroprotection under neurotoxic conditions. Given the critical role of oxidative stress in AD pathogenesis, an increase in GSTP1 level may be an alternative way to modulate Cdk5 signaling, eliminate oxidative stress, and prevent neurodegeneration.

Synthesis of Novel Indolyl-1,2,4-triazoles as Potent and Selective Anticancer Agents

Co-reporter:Dalip Kumar;Maruthi Kumar Narayanam;Kuei-Hua Chang

Chemical Biology & Drug Design 2011 Volume 77( Issue 3) pp:182-188

Publication Date(Web):

DOI:10.1111/j.1747-0285.2010.01051.x

A diverse series of 22 indolyl-1,2,4-triazole congeners (6 and 7) have been synthesized from the reaction of indole-3-carbonitrile (4) or (5) with appropriate acid hydrazides in the presence of potassium carbonate. Synthesized compounds were evaluated for their cytotoxicity against six human cancer cell lines, and some of the compounds displayed promising activity. In particular, 3-(3′,4′,5′-trimethoxyphenyl)-5-(N-methyl-3′-indolyl)-1,2,4-triazole (7i) and 3-(4′-piperidinyl)-5-(N-methyl-3′-indolyl)-1,2,4-triazole (7n) were the most promising and broadly active compounds against the tested cell lines. It was interesting to note that the trimethoxyphenyl analog 7i showed twofold selective cytotoxicity against PaCa2 cell line (IC₅₀ 0.8 μm), whereas piperidinyl analog 7n was found to be selectively cytotoxic against MCF7 cell line (IC₅₀ 1.6 μm). Notably, the 4-fluorophenyl derivative 7c exhibited selective cytotoxicity against PC3 cell line (IC₅₀ 4 μm). The structure–activity relationship study revealed that substituents including 3,4,5-trimethoxyphenyl, 3,4-dimethoxyphenyl, 4-benzyloxy-3-methoxyphenyl, 4-piperidinyl, 4-fluorophenyl and N-methylindole are beneficial for the activity of indolyl-1,2,4-triazoles (6 and 7).

One-pot synthesis and anticancer studies of 2-arylamino-5-aryl-1,3,4-thiadiazoles

Co-reporter:Dalip Kumar, Buchi Reddy Vaddula, Kuei-Hua Chang, Kavita Shah

Bioorganic & Medicinal Chemistry Letters 2011 Volume 21(Issue 8) pp:2320-2323

Publication Date(Web):15 April 2011

DOI:10.1016/j.bmcl.2011.02.083

A series of 2-arylamino-5-aryl-1,3,4-thiadiazoles 1a–j were synthesized and screened for their anticancer activity against various human cancer cell lines. The novel one-pot synthesis of 1,3,4-thiadiazoles was achieved by refluxing aryl aldehydes, hydrazine hydrate, and aryl isothiocyanates in methanol followed by oxidative cyclization with ferric ammonium sulfate. The compounds 1g–j with trimethoxyphenyl at the C-5 position displayed extremely potent anticancer activity with at least twofold selectivity (IC50: 4.3–9.2 μM). The nature of substituent on the C-2 arylamino ring may be critical in opting for the selectivity towards a particular cancer cell.

Synthesis and in-vitro anticancer activity of 3,5-bis(indolyl)-1,2,4-thiadiazoles

Co-reporter:Dalip Kumar, N. Maruthi Kumar, Kuei-Hua Chang, Ritika Gupta, Kavita Shah

Bioorganic & Medicinal Chemistry Letters 2011 21(19) pp: 5897-5900

Publication Date(Web):

DOI:10.1016/j.bmcl.2011.07.089

Synthesis and anticancer activity of 5-(3-indolyl)-1,3,4-thiadiazoles

Co-reporter:Dalip Kumar, N. Maruthi Kumar, Kuei-Hua Chang, Kavita Shah

European Journal of Medicinal Chemistry 2010 Volume 45(Issue 10) pp:4664-4668

Publication Date(Web):October 2010

DOI:10.1016/j.ejmech.2010.07.023

A series of 5-(3-indolyl)-2-substituted-1,3,4-thiadiazoles 5a–m were synthesized and their cytotoxicity analyzed against six human cancer cell lines. The reaction of indole-3-carboxylic acid 3 with aryl or heteroaryl hydrazides afforded the N,N′-diacylhydrazines 4, which upon treatment with Lawesson’s reagent resulted in the formation of indolyl-1,3,4-thiadiazoles 5a–m in good yields. Indolyl-1,3,4-thiadiazole 5m with 4-benzyloxy-3-methoxyphenyl and 5-bromo indolyl substituents is the most active in suppressing the growth of cancer cells (IC50 1.5 μM, PaCa2). The compounds 5b, 5e and 5h bearing C-2 substituent as benzyl, 3,4-dimethoxyphenyl and 4-benzyloxy-3-methoxyphenyl, respectively, have shown significant cytotoxicity against multiple cancer cell lines. Introduction of 4-dimethylamino (5d and 5k) and 3,4,5-trimethoxy (5l) groups in the C-2 phenyl ring induced selectivity against MCF7 and MDA-MB-231 cancer cell lines (compounds 5d, 5k and 5l).

Cdk5 is a major regulator of p38 cascade: relevance to neurotoxicity in Alzheimers disease

Co-reporter:Kuei-Hua Chang;Yola De Pablo;Hyun-pil Lee;Hyoung-gon Lee;Mark A. Smith

Journal of Neurochemistry 2010 Volume 113( Issue 5) pp:1221-1229

Publication Date(Web):

DOI:10.1111/j.1471-4159.2010.06687.x

J. Neurochem. (2010) 113, 1221–1229.

Abstract

Cyclin-dependent kinase (Cdk) 5 and p38 activities are significantly increased in Alzheimer’s Disease (AD). Both p38 and Cdk5 promote neurodegeneration upon deregulation. However, to date the mechanistic link between Cdk5 and p38 remains unclear. This study presents the first mechanism showing Cdk5 as a major regulator of p38 cascade in neurons and in transgenic mouse model of AD. Using β-amyloid and glutamate as the neurotoxic stimuli, our results show that deregulated Cdk5 induces p38 activation by increasing reactive oxygen species (ROS) in neuronal cells and in primary cortical neurons. Elimination of ROS inhibits p38 activation, revealing ROS as major stimuli of the p38 cascade. Importantly, Cdk5-mediated p38 activation increases c-Jun expression, thereby revealing a mechanistic link between deregulated Cdk5 and c-Jun level in AD brains. c-Jun is over-expressed in AD, and is believed to contribute significantly to neurodegeneration. Based on the proposed mechanism, Cdk5 inhibition is more neuroprotective relative to p38 and c-Jun, suggesting that Cdk5 is an upstream regulator of neurodegenerative pathways triggered by p38 and a preferable therapeutic target for AD.

An expeditious synthesis and anticancer activity of novel 4-(3′-indolyl)oxazoles

Co-reporter:Dalip Kumar, N. Maruthi Kumar, Swapna Sundaree, Emmanuel O. Johnson, Kavita Shah

European Journal of Medicinal Chemistry 2010 Volume 45(Issue 3) pp:1244-1249

Publication Date(Web):March 2010

DOI:10.1016/j.ejmech.2009.12.024

A series of 4-(3′-indolyl)oxazole congeners have been synthesized and studied for their cytotoxicity against six cancer cell lines. Reaction of 3-acetyl-1′-benzenesulfonylindole with [hydroxy(tosyloxy)iodo]benzene afforded pure 3-tosyloxyacetyl-1′-benzenesulfonylindole. Microwave-accelerated neat reaction of 3-tosyloxyacetyl-1-benzenesulfonylindole with amides resulted in the exclusive formation of 4-(1′-benzenesulfonylindol-3′-yl)-2-substituted oxazoles (4) in very good yield. Treatment of 4 with aqueous sodium hydroxide under refluxing conditions afforded pure 4-(3′-indolyl)-2-substituted oxazoles (5) in excellent yield. The 4-(3′-indolyl)oxazoles 5d and 11 were found to be most cytotoxic and selective against various cancer cell lines. Compounds 5g, 5j and 5l showed moderate anticancer activity.A novel series of 4-(3′-indolyl)oxazoles have been synthesized and evaluated for their cytotoxicity.

Synthesis and anticancer activities of novel 3,5-disubstituted-1,2,4-oxadiazoles

Co-reporter:Dalip Kumar, Gautam Patel, Emmanuel O. Johnson, Kavita Shah

Bioorganic & Medicinal Chemistry Letters 2009 Volume 19(Issue 10) pp:2739-2741

Publication Date(Web):15 May 2009

DOI:10.1016/j.bmcl.2009.03.158

A series of 3,5-disubstituted-1,2,4-oxadiazoles were synthesized and evaluated for their in vitro anti-proliferative activities against various cancer cell lines. Formation of 1,2,4-oxadiazole ring was accomplished by the reaction of amidoxime with carboxylic acids. The in vitro cytotoxic effects of 3,5-disubstituted-1,2,4-oxadiazoles have been demonstrated across a wide array of tumor cell types and a few compounds exhibited specificity towards pancreatic (3f, 3h, 3j, and 3k) and prostate (3n) cancer cells. Among the prepared 3,5-disubstituted-1,2,4-oxadiazoles, compound 3n is the most selective (>450-fold) and compound 3p is the most cytotoxic (10 nM) against prostate cancer cell lines.A library of 3,5-disubstituted-1,2,4-oxadiazoles were synthesized and evaluated for their in vitro anti-proliferative activities against various cancer cell lines. The series resulted in the identification of the most selective compound 3n (>450-fold for LnCaP) and the most potent compound 3p (9 nM, for LnCaP) along with several new cytotoxic agents.

Deregulated Cdk5 promotes oxidative stress and mitochondrial dysfunction

Co-reporter:Kai-Hui Sun;Yola De Pablo;Fabien Vincent

Journal of Neurochemistry 2008 Volume 107( Issue 1) pp:265-278

Publication Date(Web):

DOI:10.1111/j.1471-4159.2008.05616.x

Abstract

Oxidative stress is one of the earliest events in Alzheimer’s disease (AD). A chemical genetic screen revealed that deregulated cyclin-dependent kinase 5 (Cdk5) may cause oxidative stress by compromising the cellular anti-oxidant defense system. Using novel Cdk5 modulators, we show the mechanism by which Cdk5 can induce oxidative stress in the disease’s early stage and cell death in the late stage. Cdk5 dysregulation upon neurotoxic insults results in reactive oxygen species (ROS) accumulation in neuronal cells because of the inactivation of peroxiredoxin I and II. Sole temporal activation of Cdk5 also increases ROS, suggesting its major role in this process. Cdk5 inhibition rescues mitochondrial damage upon neurotoxic insults, thereby revealing Cdk5 as an upstream regulator of mitochondrial dysfunction. As mitochondrial damage results in elevated ROS and Ca²⁺ levels, both of which activate Cdk5, we propose that a feedback loop occurs in late stage of AD and leads to cell death (active Cdk5 ROS excess ROS mitochondrial damage ROS hyperactive Cdk5 severe oxidative stress and cell injury cell death). Cdk5 inhibition upon neurotoxic insult prevents cell death significantly, supporting this hypothesis. As oxidative stress and mitochondrial dysfunction play pivotal roles in promoting neurodegeneration, Cdk5 could be a viable therapeutic target for AD.

Engineering Unnatural Nucleotide Specificity to Probe G Protein Signaling

Co-reporter:Fabien Vincent, Silas P. Cook, Emmanuel O. Johnson, Dana Emmert, Kavita Shah

Chemistry & Biology 2007 Volume 14(Issue 9) pp:1007-1018

Publication Date(Web):21 September 2007

DOI:10.1016/j.chembiol.2007.08.006

G proteins comprise ∼0.5% of proteins encoded by mammalian genomes. To date, there exists a lack of small-molecule modulators that could contribute to their functional study. In this report, we present the use of H-Ras to develop a system that answers this need. Small molecules that allow for the highly specific inhibition or activation of the engineered G protein were developed. The rational design preserved binding of the natural substrates to the G protein, and the mutations were functionally innocuous in a cellular context. This tool can be used for isolating specific G protein effectors, as we demonstrate with the identification of Nol1 as a putative effector of H-Ras. Finally, the generalization of this system was confirmed by applying it to Rap1B, suggesting that this method will be applicable to other G proteins.

Design, synthesis and in vitro cytotoxicity studies of novel β-carbolinium bromides

Co-reporter:P.O. Venkataramana Reddy, Shriprada Mishra, Mukund P. Tantak, Kumar Nikhil, Rachna Sadana, Kavita Shah, Dalip Kumar

Bioorganic & Medicinal Chemistry Letters (15 March 2017) Volume 27(Issue 6) pp:

Publication Date(Web):15 March 2017

DOI:10.1016/j.bmcl.2017.02.010

A series of novel β-carbolinium bromides has been synthesized from easily accessible β-carbolines and 1-aryl-2-bromoethanones. The newly synthesized compounds were evaluated for their in vitro anticancer activity. Among the synthesized derivatives, compounds 16l, 16o and 16s exhibited potent anticancer activity with IC50 values of <10 μM against tested cancer cell lines. The most potent analogue 16l was broadly active against all the tested cancer cell lines (IC50 = 3.16–7.93 μM). In order to test the mechanism of cell death, we exposed castration resistant prostate cancer cell line (C4-2) to compounds 16l and 16s, which resulted in increased levels of cleaved PARP1 and AO/EB staining, indicating that β-carbolinium salts induce apoptosis in these cells. Additionally, the most potent β-carbolines 16l and 16s were found to inhibit tubulin polymerization.