Synthesis, Spectral Analysis, in vitro Evaluation and Molecular Docking of 4-Chloro-1H-pyrrolo[2,3-b]pyridine-3-amines as Anticancer Agents

Yadala Prapurna Chandra; Shaik Asma Parveen; Beebi Jan Kalluri; Y. Sribharathi; Guntaka Ramachandra Reddy

doi:10.14233/ajchem.2026.35812

Issue

Vol. 38 No. 5 (2026): Vol 38, Issue 5, 2026

Issue Published : 4 May 2026

This work is licensed under a Creative Commons Attribution 4.0 International License.

Synthesis, Spectral Analysis, in vitro Evaluation and Molecular Docking of 4-Chloro-1H-pyrrolo[2,3-b]pyridine-3-amines as Anticancer Agents

https://doi.org/10.14233/ajchem.2026.35812

Yadala Prapurna Chandra

Ratnam Institute of Pharmacy, Pidathapolur, Nellore-524411, India

https://orcid.org/0009-0002-5749-6038

Shaik Asma Parveen

Ratnam Institute of Pharmacy, Pidathapolur, Nellore-524411, India

https://orcid.org/0009-0001-2155-0840

Beebi Jan Kalluri

Department of Pharmaceutical Analysis, Ratnam Institute of Pharmacy, Pidathapolur, Nellore-524411, India

https://orcid.org/0009-0005-7872-1400

Y. Sribharathi

Ratnam Institute of Pharmacy, Pidathapolur, Nellore-524411, India

https://orcid.org/0009-0000-6770-8976

Guntaka Ramachandra Reddy

Faculty of Pharmacy, Sree Balaji Medical College Hospital, Chennai-600044, India

https://orcid.org/0009-0000-6501-732X

Corresponding Author(s) : Shaik Asma Parveen

asmaparveen.shk@gmail.com

Asian Journal of Chemistry, Vol. 38 No. 5 (2026): Vol 38, Issue 5, 2026
Article Published : 4 May 2026

Abstract

Azaindole-based scaffolds are recognised for their diverse pharmacological properties, including anticancer, anti-angiogenic, antioxidant, antibacterial, antifungal and anti-inflammatory activities. In present study, a novel series of 4-chloro-1H-pyrrolo[2,3-b]pyridine-3-amine derivatives was synthesised and characterised to investigate their potential as poly(ADP-ribose) polymerase-1 (PARP1) inhibitors for anticancer therapy. The synthesised derivatives were evaluated for anticancer activity against MCF-7 breast cancer cell lines using the MTT assay method. Among the tested compounds, 5b, 5g, 5h and 5a demonstrated notable cytotoxic activity against breast cancer cells. The molecular docking studies were further performed against the PARP1 target protein (PDB ID: 7KK4) to examine ligand–protein interactions and binding affinity. The computational analysis revealed that compounds 5e and 5c exhibited favourable binding interactions within the active site, suggesting their potential as promising PARP1 inhibitory candidates for further anticancer investigations.

Keywords

Chloroazaindole Phenylamine derivatives Pyrrolo-pyridine amines PARP1 Inhibitors Anticancer activity

(1)

Chandra, Y. P.; Parveen, S. A.; Kalluri, B. J.; Sribharathi, Y.; Reddy, G. R. Synthesis, Spectral Analysis, in Vitro Evaluation and Molecular Docking of 4-Chloro-1H-pyrrolo[2,3-b]pyridine-3-Amines As Anticancer Agents. ajc 2026, 38, 1361-1366.

Download Citation

References

J. Merour and B. Joseph, Curr. Org. Chem., 5, 471 (2001); https://doi.org/10.2174/1385272013375427.
J.Y. Mérour, F. Buron, K. Plé, P. Bonnet and S. Routier, Molecules, 19, 19935 (2014); https://doi.org/10.3390/molecules191219935
Y. Kotaiah, N. Harikrishna, K. Nagaraju and C. Venkata Rao, Eur. J. Med. Chem., 58, 340 (2012); https://doi.org/10.1016/j.ejmech.2012.10.007
R. Tyagi, K. Yadav, N. Srivastava and R. Sagar, Curr. Pharm. Design, 30, 255 (2024); https://doi.org/10.2174/0113816128280082231205071504.
P.G. Jain and B.D. Patel, Eur. J. Med. Chem., 165, 198 (2019); https://doi.org/10.1016/j.ejmech.2019.01.024
R. Cincinelli, L. Musso, L. Merlini, G. Giannini, L. Vesci, F.M. Milazzo, N. Carenini, P. Perego, S. Penco, R. Artali, F. Zunino, C. Pisano and S. Dallavalle, Bioorg. Med. Chem., 22, 1089 (2014); https://doi.org/10.1016/j.bmc.2013.12.031
C. Marminon, A. Pierré, B. Pfeiffer, V. Pérez, S. Léonce, A. Joubert, C. Bailly, P. Renard, J. Hickman and M. Prudhomme, J. Med. Chem., 46, 609 (2003); https://doi.org/10.1021/jm0210055
M.A. El-Zahabi, R. Yousef, I. Eissa and A. Elwan, Al-Azhar J. Pharm. Sci., 68, 64 (2023); https://doi.org/10.21608/ajps.2023.332167
H. Behbehani, F.A. Aryan, K.M. Dawood and H.M. Ibrahim, Sci. Rep., 10, 21691 (2020); https://doi.org/10.1038/s41598-020-78590-x
A.S. Borude, S.R. Deshmukh, S.V. Tiwari, S.H. Kumar and S.R. Thopate, Eur. J. Med. Chem., 276, 116727 (2024); https://doi.org/10.1016/j.ejmech.2024.116727
R. Wang, Y. Chen, B. Yang, S. Yu, X. Zhao, C. Zhang, C. Hao, D. Zhao and M. Cheng, Bioorg. Chem., 94, 103474 (2020); https://doi.org/10.1016/j.bioorg.2019.103474
M. Alrooqi, S. Khan, F.A. Alhumaydhi, S.A. Asiri, M. Alshamrani, M.M. Mashraqi, A. Alzamami, A.M. Alshahrani and A.A. Aldahish, Anticancer. Agents Med. Chem., 22, 2775 (2022); https://doi.org/10.2174/1871520622666220324102849
L. Long, H. Zhang, Z.H. Zhou, L. Duan, D. Fan, R. Wang, S. Xu, D. Qiao and W. Zhu, Eur. J. Med. Chem., 273, 116470 (2024); https://doi.org/10.1016/j.ejmech.2024.116470
B. Morak-Młodawska, E. Martula, M. Jeleń, A. Beberok, Z. Rzepka, S. Musiał, S. Małek, M. Karkoszka-Stanowska and D. Wrześniok, Molecules, 30, 2779 (2025); https://doi.org/10.3390/molecules30132779
T.Y. Shen, T.B. Windholz, A. Rosegay, B.E. Witzel, A.N. Wilson, J.D. Willett, W.J. Holtz, R.L. Ellis, A.R. Matzuk, S. Lucas, C.H. Stammer, F.W. Holly, L.H. Sarett, E.A. Risley, G.W. Nuss and C.A. Winter, J. Am. Chem. Soc., 85, 488 (1963); https://doi.org/10.1021/ja00887a038
R. Prudent, É. Vassal-Stermann, C.H. Nguyen, M. Mollaret, J. Viallet, A. Desroches-Castan, A. Martinez, C. Barette, C. Pillet, G. Valdameri, E. Soleilhac, A. Di Pietro, J.-J. Feige, M. Billaud, J.-C. Florent and L. Lafanechère, Br. J. Pharmacol., 168, 673 (2013); https://doi.org/10.1111/j.1476-5381.2012.02230.x.
R. Pettipher, T.T. Hansel and R. Armer, Nat. Rev. Drug Discov., 6, 313 (2007); https://doi.org/10.1038/nrd2266
L. Zan, H. Wu, J. Jiang, S. Zhao, Y. Song, G. Teng, H. Li, Y. Jia, M. Zhou, X. Zhang, J. Qi and J. Wang, Neurochem. Int., 58, 872 (2011); https://doi.org/10.1016/j.neuint.2011.02.014
S. Rekulapally, R. Jarapula, K. Gangarapu, S. Manda and J.R. Vaidya, Med. Chem. Res., 24, 3412 (2015); https://doi.org/10.1007/s00044-015-1390-0
J. Guillard, M. Decrop, N. Gallay, C. Espanel, E. Boissier, O. Herault and M.-C. Viaud-Massuard, Bioorg. Med. Chem. Lett., 17, 1934 (2007); https://doi.org/10.1016/j.bmcl.2007.01.033
M. Lefoix, G. Coudert, S. Routier, B. Pfeiffer, D.H. Caignard, J. Hickman, A. Pierré, R.M. Golsteyn, S. Léonce, C. Bossard and J.-Y. Mérour, Bioorg. Med. Chem., 16, 5303 (2008); https://doi.org/10.1016/j.bmc.2008.02.086
D.A. Sandham, C. Adcock, K. Bala, L. Barker, Z. Brown, G. Dubois, D. Budd, B. Cox, R.A. Fairhurst, M. Furegati, C. Leblanc, J. Manini, R. Profit, J. Reilly, R. Stringer, A. Schmidt, K.L. Turner, S.J. Watson, J. Willis, G. Williams and C. Wilson, Bioorg. Med. Chem. Lett., 19, 4794 (2009); https://doi.org/10.1016/j.bmcl.2009.06.042
A. Chen, Chin. J. Cancer, 30, 463 (2011); https://doi.org/10.5732/cjc.011.10111
N. Sharma and Anurag, Mini Rev. Med. Chem., 19, 727 (2019); https://doi.org/10.2174/1389557518666180928154004
Y.Q. Wang, P.Y. Wang, Y.T. Wang, G.F. Yang, A. Zhang and Z.H. Miao, J. Med. Chem., 59, 9575 (2016); https://doi.org/10.1021/acs.jmedchem.6b00055.
Z. Zhong, L. Shi, T. Fu, J. Huang and Z. Pan, J. Med. Chem., 65, 7278 (2022); https://doi.org/10.1021/acs.jmedchem.2c00255
K. Ryan, B. Bolaňos, M. Smith, P.B. Palde, P.D. Cuenca, T.L. Van Arsdale, S. Niessen, L. Zhang, D. Behenna, M.A. Ornelas, K.T. Tran, S. Kaiser, L. Lum, A. Stewart and K.S. Gajiwala, J. Biol. Chem., 296, 100251 (2021); https://doi.org/10.1074/jbc.RA120.016573
BIOVIA, Dassault Systèmes, Discovery Studio Visualizer, ver. 21.1.0.20298, San Diego, CA, USA: Dassault Systèmes (2021).

References

J. Merour and B. Joseph, Curr. Org. Chem., 5, 471 (2001); https://doi.org/10.2174/1385272013375427.

J.Y. Mérour, F. Buron, K. Plé, P. Bonnet and S. Routier, Molecules, 19, 19935 (2014); https://doi.org/10.3390/molecules191219935

Y. Kotaiah, N. Harikrishna, K. Nagaraju and C. Venkata Rao, Eur. J. Med. Chem., 58, 340 (2012); https://doi.org/10.1016/j.ejmech.2012.10.007

R. Tyagi, K. Yadav, N. Srivastava and R. Sagar, Curr. Pharm. Design, 30, 255 (2024); https://doi.org/10.2174/0113816128280082231205071504.

P.G. Jain and B.D. Patel, Eur. J. Med. Chem., 165, 198 (2019); https://doi.org/10.1016/j.ejmech.2019.01.024

R. Cincinelli, L. Musso, L. Merlini, G. Giannini, L. Vesci, F.M. Milazzo, N. Carenini, P. Perego, S. Penco, R. Artali, F. Zunino, C. Pisano and S. Dallavalle, Bioorg. Med. Chem., 22, 1089 (2014); https://doi.org/10.1016/j.bmc.2013.12.031

C. Marminon, A. Pierré, B. Pfeiffer, V. Pérez, S. Léonce, A. Joubert, C. Bailly, P. Renard, J. Hickman and M. Prudhomme, J. Med. Chem., 46, 609 (2003); https://doi.org/10.1021/jm0210055

M.A. El-Zahabi, R. Yousef, I. Eissa and A. Elwan, Al-Azhar J. Pharm. Sci., 68, 64 (2023); https://doi.org/10.21608/ajps.2023.332167

H. Behbehani, F.A. Aryan, K.M. Dawood and H.M. Ibrahim, Sci. Rep., 10, 21691 (2020); https://doi.org/10.1038/s41598-020-78590-x

A.S. Borude, S.R. Deshmukh, S.V. Tiwari, S.H. Kumar and S.R. Thopate, Eur. J. Med. Chem., 276, 116727 (2024); https://doi.org/10.1016/j.ejmech.2024.116727

R. Wang, Y. Chen, B. Yang, S. Yu, X. Zhao, C. Zhang, C. Hao, D. Zhao and M. Cheng, Bioorg. Chem., 94, 103474 (2020); https://doi.org/10.1016/j.bioorg.2019.103474

M. Alrooqi, S. Khan, F.A. Alhumaydhi, S.A. Asiri, M. Alshamrani, M.M. Mashraqi, A. Alzamami, A.M. Alshahrani and A.A. Aldahish, Anticancer. Agents Med. Chem., 22, 2775 (2022); https://doi.org/10.2174/1871520622666220324102849

L. Long, H. Zhang, Z.H. Zhou, L. Duan, D. Fan, R. Wang, S. Xu, D. Qiao and W. Zhu, Eur. J. Med. Chem., 273, 116470 (2024); https://doi.org/10.1016/j.ejmech.2024.116470

B. Morak-Młodawska, E. Martula, M. Jeleń, A. Beberok, Z. Rzepka, S. Musiał, S. Małek, M. Karkoszka-Stanowska and D. Wrześniok, Molecules, 30, 2779 (2025); https://doi.org/10.3390/molecules30132779

T.Y. Shen, T.B. Windholz, A. Rosegay, B.E. Witzel, A.N. Wilson, J.D. Willett, W.J. Holtz, R.L. Ellis, A.R. Matzuk, S. Lucas, C.H. Stammer, F.W. Holly, L.H. Sarett, E.A. Risley, G.W. Nuss and C.A. Winter, J. Am. Chem. Soc., 85, 488 (1963); https://doi.org/10.1021/ja00887a038

R. Prudent, É. Vassal-Stermann, C.H. Nguyen, M. Mollaret, J. Viallet, A. Desroches-Castan, A. Martinez, C. Barette, C. Pillet, G. Valdameri, E. Soleilhac, A. Di Pietro, J.-J. Feige, M. Billaud, J.-C. Florent and L. Lafanechère, Br. J. Pharmacol., 168, 673 (2013); https://doi.org/10.1111/j.1476-5381.2012.02230.x.

R. Pettipher, T.T. Hansel and R. Armer, Nat. Rev. Drug Discov., 6, 313 (2007); https://doi.org/10.1038/nrd2266

L. Zan, H. Wu, J. Jiang, S. Zhao, Y. Song, G. Teng, H. Li, Y. Jia, M. Zhou, X. Zhang, J. Qi and J. Wang, Neurochem. Int., 58, 872 (2011); https://doi.org/10.1016/j.neuint.2011.02.014

S. Rekulapally, R. Jarapula, K. Gangarapu, S. Manda and J.R. Vaidya, Med. Chem. Res., 24, 3412 (2015); https://doi.org/10.1007/s00044-015-1390-0

J. Guillard, M. Decrop, N. Gallay, C. Espanel, E. Boissier, O. Herault and M.-C. Viaud-Massuard, Bioorg. Med. Chem. Lett., 17, 1934 (2007); https://doi.org/10.1016/j.bmcl.2007.01.033

M. Lefoix, G. Coudert, S. Routier, B. Pfeiffer, D.H. Caignard, J. Hickman, A. Pierré, R.M. Golsteyn, S. Léonce, C. Bossard and J.-Y. Mérour, Bioorg. Med. Chem., 16, 5303 (2008); https://doi.org/10.1016/j.bmc.2008.02.086

D.A. Sandham, C. Adcock, K. Bala, L. Barker, Z. Brown, G. Dubois, D. Budd, B. Cox, R.A. Fairhurst, M. Furegati, C. Leblanc, J. Manini, R. Profit, J. Reilly, R. Stringer, A. Schmidt, K.L. Turner, S.J. Watson, J. Willis, G. Williams and C. Wilson, Bioorg. Med. Chem. Lett., 19, 4794 (2009); https://doi.org/10.1016/j.bmcl.2009.06.042

A. Chen, Chin. J. Cancer, 30, 463 (2011); https://doi.org/10.5732/cjc.011.10111

N. Sharma and Anurag, Mini Rev. Med. Chem., 19, 727 (2019); https://doi.org/10.2174/1389557518666180928154004

Y.Q. Wang, P.Y. Wang, Y.T. Wang, G.F. Yang, A. Zhang and Z.H. Miao, J. Med. Chem., 59, 9575 (2016); https://doi.org/10.1021/acs.jmedchem.6b00055.

Z. Zhong, L. Shi, T. Fu, J. Huang and Z. Pan, J. Med. Chem., 65, 7278 (2022); https://doi.org/10.1021/acs.jmedchem.2c00255

K. Ryan, B. Bolaňos, M. Smith, P.B. Palde, P.D. Cuenca, T.L. Van Arsdale, S. Niessen, L. Zhang, D. Behenna, M.A. Ornelas, K.T. Tran, S. Kaiser, L. Lum, A. Stewart and K.S. Gajiwala, J. Biol. Chem., 296, 100251 (2021); https://doi.org/10.1074/jbc.RA120.016573

BIOVIA, Dassault Systèmes, Discovery Studio Visualizer, ver. 21.1.0.20298, San Diego, CA, USA: Dassault Systèmes (2021).

Author biographies is not available.