European Journal of Chemistry 2018, 9(4), 322-330. doi:10.5155/eurjchem.9.4.322-330.1748

Quinazolin derivatives as emerging alpha-glucosidase inhibitors


Ashok Reddy Ankireddy (1) orcid , Rambabu Gundla (2,*) orcid , Tuniki Balaraju (3) orcid , Venkanna Banothu (4) orcid , Krishna Prasad Gundla (5) orcid , Uma Addepally (6) orcid , Jithendra Chimakurthy (7) orcid

(1) Department of Chemistry, Gitam University, Hyderabad, Rudraram Mandal, Sangareddy District, Patancheru, Hyderabad, Telangana 502329, India
(2) Department of Chemistry, Gitam University, Hyderabad, Rudraram Mandal, Sangareddy District, Patancheru, Hyderabad, Telangana 502329, India
(3) Department of Chemistry, Birla Institute of Technology, Mesra, Jharkhand 835215, India
(4) Centre for Biotechnology (CBT), Institute of Science & Technology (IST), Jawaharlal Nehru Technological University Hyderabad (JNTUH), Kukatpally, Hyderabad, Telangana State, 500085, India
(5) Department of Chemistry, Gitam University, Hyderabad, Rudraram Mandal, Sangareddy District, Patancheru, Hyderabad, Telangana 502329, India
(6) Centre for Biotechnology (CBT), Institute of Science & Technology (IST), Jawaharlal Nehru Technological University Hyderabad (JNTUH), Kukatpally, Hyderabad, Telangana State, 500085, India
(7) Department of Pharmaceutical Sciences, Vignan’s Foundation for Science, Technology and Research Vadlamudi, Guntur, Andhra Pradesh 522213, India
(*) Corresponding Author

Received: 29 May 2018, Accepted: 06 Sep 2018, Published: 31 Dec 2018

Abstract


A series of C-7 substituted-2-morpholino-N-(pyridin-2-ylmethyl)quinazolin-4-amine have been synthesized and biochemical assay was examined against α-glucosidase function inhibition activity. A structure activity and structure property relationship study was experimented to surface the new hit compound. This study led to the identification of C-7substituted quinazolines with minimum inhibitory concentrations (MICs) in the preffered micromolar range in addition with interesting physicochemical properties. Biological evaluation yielded eight analogs which rose with significant α-glucosidase inhibition potency (IC50 values < 2 μM, where reference compound (Acarbose) potency value is IC50 = 0.586 uM) and could be promising candidates for further lead optimization.


Keywords


Diabetes; Acarbose; Inhibitors; Inflammation; Alpha-glucosidase; Quninazoline derivatives

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DOI: 10.5155/eurjchem.9.4.322-330.1748

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References

[1]. Geiss, L. S.; Wang, J.; Cheng, Y. J.; Thompson, T. J.; Barker, L.; Li, Y.; Albright, A. L.; Gregg, E. W. Jama 2014, 312, 1218-1226.
https://doi.org/10.1001/jama.2014.11494

[2]. Ferreres, F.; Gil-Izquierdo, A.; Vinholes, J.; Silva, S. T.; Valentao, P.; Andrade, P. B. Food Chem. 2012, 134, 894-904.
https://doi.org/10.1016/j.foodchem.2012.02.201

[3]. Bruni, C.; Sica, V.; Auricchio, F.; Covelli, I. Biochim. Biophys. Acta (BBA)-Enzymol. 1970, 212, 470-477.

[4]. Garlapati, R.; Pottabathini, N.; Gurram, V.; Chaudhary, A. B.; Chunduri, V. R.; Patro, B. Tetrahedron Lett. 2012, 53, 5162-5166.
https://doi.org/10.1016/j.tetlet.2012.07.061

[5]. Garlapati, R.; Pottabathini, N.; Gurram, V.; Kasani, K. S.; Gundla, R.; Thulluri, C.; Machiraju, P. K.; Chaudhary, A. B.; Addepally, U.; Dayam, R. Org. Biomol. Chem. 2013, 11, 4778-4791.
https://doi.org/10.1039/c3ob40636a

[6]. Chandrika, P. M.; Yakaiah, T.; Rao, A. R. R.; Narsaiah, B.; Reddy, N. C.; Sridhar, V.; Rao, J. V. Eur. J. Med. Chem. 2008, 43, 846-852.
https://doi.org/10.1016/j.ejmech.2007.06.010

[7]. Ram, V. J.; Tripathi, B. K.; Srivastava, A. K. Bioorg. Med. Chem. 2003, 11, 2439-2444.
https://doi.org/10.1016/S0968-0896(03)00142-1

[8]. Koh, K. K.; Park, S. M.; Quon, M. J. Circulation 2008, 117, 3238-3249.
https://doi.org/10.1161/CIRCULATIONAHA.107.741645

[9]. Saltiel, A. R.; Olefsky, J. M. Diabetes 1996, 45, 1661-1669.
https://doi.org/10.2337/diab.45.12.1661

[10]. De Melo, E. B.; Gomes, A. S.; Carvalho, I. Tetrahedron 2006, 62, 10277-10302.
https://doi.org/10.1016/j.tet.2006.08.055

[11]. Landgraf, R. Drugs Aging 2000, 17, 411-425.
https://doi.org/10.2165/00002512-200017050-00007

[12]. Sinclair, A. J. International textbook of Diabetes mellitus, Wiley, Worcestershire, United Kingdom, 2004.

[13]. Wan, Z. K.; Wacharasindhu, S.; Levins, C. G.; Lin, M.; Tabei, K.; Mansour, T. S. J. Org. Chem. 2007, 72, 10194-10210.
https://doi.org/10.1021/jo7020373

[14]. Goto, S.; Tsuboi, H.; Kanoda, M.; Mukai, K.; Kagara, K. Org. Proc. Res. Dev. 2003, 7, 700-706.
https://doi.org/10.1021/op0340661

[15]. Friesner, R. A.; Murphy, R. B.; Repasky, M. P.; Frye, L. L.; Greenwood, J. R.; Halgren, T. A.; Sanschagrin, P. C.; Mainz, D. T. J. Med. Chem. 2006, 49, 6177-6196.
https://doi.org/10.1021/jm051256o

[16]. Rosenstock, J.; Brazg, R.; Andryuk, P. J.; Lu, K.; Stein, P.; Study, S. Clin. Therap. 2006, 28, 1556-1568.
https://doi.org/10.1016/j.clinthera.2006.10.007

[17]. Yamaguchi, T.; Sakairi, K.; Yamaguchi, E.; Tada, N.; Itoh, A. RSC Adv. 2016, 6, 56892-56895.
https://doi.org/10.1039/C6RA04073J

[18]. Ghavami, A.; Johnston, B. D.; Pinto, B. M. J. Org. Chem. 2001, 66, 2312-2317.
https://doi.org/10.1021/jo001444g

[19]. Andrews, J. S.; Weimar, T.; Frandsen, T. P.; Svensson, B.; Pinto, B. M. J. Am. Chem. Soc. 1995, 117, 10799-10804.
https://doi.org/10.1021/ja00149a002

[20]. Flanagan, P. R.; Forstner, G. G. Biochem. J. 1978, 173, 553-563.
https://doi.org/10.1042/bj1730553

[21]. Balaraju, T.; Kumar, A.; Bal, C.; Chattopadhyay, D.; Jena, N.; Bal, N. C.; Sharon, A. Struc. Chem. 2013, 24, 1499-1512.
https://doi.org/10.1007/s11224-012-0181-1

[22]. Khan, I.; Ibrar, A.; Abbas, N.; Saeed, A. Eur. J. Med. Chem. 2014, 76, 193-244.
https://doi.org/10.1016/j.ejmech.2014.02.005

[23]. Gurram, V.; Garlapati, R.; Thulluri, C.; Madala, N.; Kasani, K. S.; Machiraju, P. K.; Doddapalla, R.; Addepally, U.; Gundla, R.; Patro, B. Med. Chem. Res. 2015, 24, 2227-2237.
https://doi.org/10.1007/s00044-014-1293-5

[24]. Iino, T.; Sasaki, Y.; Bamba, M.; Mitsuya, M.; Ohno, A.; Kamata, K.; Hosaka, H.; Maruki, H.; Futamura, M.; Yoshimoto, R. Bioorg. Med. Chem. Lett. 2009, 19, 5531-5538.
https://doi.org/10.1016/j.bmcl.2009.08.064

[25]. Thiyagarajan, A.; Salim, M. T.; Balaraju, T.; Bal, C.; Baba, M.; Sharon, A. Bioorg. Med. Chem. Lett. 2012, 22, 7742-7747.
https://doi.org/10.1016/j.bmcl.2012.09.072

[26]. Gurram, V.; Akula, H. K.; Garlapati, R.; Pottabathini, N.; Lakshman, M. K. Adv. Syn. Catal. 2015, 357, 451-462.
https://doi.org/10.1002/adsc.201400889

[27]. Liu, J. F.; Lee, J.; Dalton, A. M.; Bi, G.; Yu, L.; Baldino, C. M.; McElory, E.; Brown, M. Tetrahedron Lett. 2005, 46, 1241-1244.
https://doi.org/10.1016/j.tetlet.2005.01.008

[28]. Hikawa, H.; Ino, Y.; Suzuki, H.; Yokoyama, Y. J. Org. Chem. 2012, 77, 7046-7051.
https://doi.org/10.1021/jo301282n

[29]. Garlapati, R.; Pottabathini, N.; Gurram, V.; Kasani, K. S.; Gundla, R.; Thulluri, C.; Machiraju, P. K.; Chaudhary, A. B.; Addepally, U.; Dayam, R.; Chunduri, V. R.; Patro, B. Org. Biomol. Chem. 2013, 11, 4778-4791.
https://doi.org/10.1039/c3ob40636a

[30]. Kasula, M.; Balaraju, T.; Toyama, M.; Thiyagarajan, A.; Bal, C.; Baba, M.; Sharon, A. Chem. Med. Chem. 2013, 8, 1673-1680.

[31]. Balaraju, T.; Kumar, A.; Bal, C.; Chattopadhyay, D.; Jena, N.; Bal, N. C.; Sharon, A. Struc. Chem. 2013, 24(5), 1499-1512.
https://doi.org/10.1007/s11224-012-0181-1

[32]. Bal, N. C.; Jena, N.; Sopariwala, D.; Balaraju, T.; Shaikh, S.; Bal, C.; Sharon, A.; Gyorke, S.; Periasamy, M. Biochem. J. 2011, 435(2), 391-399.
https://doi.org/10.1042/BJ20101771

[33]. Thiyagarajan, A.; Salim, M. T. A.; Balaraju, T.; Bal, C.; Baba, M.; Sharon, A. Bioorg. Med. Chem. Lett. 2012, 22(24), 7742-7747.
https://doi.org/10.1016/j.bmcl.2012.09.072

[34]. Kumar, A.; Chakravarty, H.; Bal, N. C.; Balaraju, T.; Jena, N.; Misra, G.; Bal, C.; Balaraju, T.; Jena, N.; Misra, G.; Pieroni, E.; Periasamy, M.; Sharon, A. Mol. Biosys. 2013, 9(7), 1949-1957.
https://doi.org/10.1039/c3mb25588c

[35]. Bal, N. C.; Jena, N.; Chakravarty, H.; Kumar, A.; Chi, M.; Balaraju, T.; Rawale, S. V.; Sharon, A.; Periasamy, M. Biopolymers 2015, 103(1), 15-22.
https://doi.org/10.1002/bip.22534

[36]. Talasila, M.; Bavirisetti, H.; Chimakurthy, J.; Candasamy, M. J. Health Sci. 2014, 4(3), 162-168.
https://doi.org/10.17532/jhsci.2014.163


How to cite


Ankireddy, A.; Gundla, R.; Balaraju, T.; Banothu, V.; Gundla, K.; Addepally, U.; Chimakurthy, J. Eur. J. Chem. 2018, 9(4), 322-330. doi:10.5155/eurjchem.9.4.322-330.1748
Ankireddy, A.; Gundla, R.; Balaraju, T.; Banothu, V.; Gundla, K.; Addepally, U.; Chimakurthy, J. Quinazolin derivatives as emerging alpha-glucosidase inhibitors. Eur. J. Chem. 2018, 9(4), 322-330. doi:10.5155/eurjchem.9.4.322-330.1748
Ankireddy, A., Gundla, R., Balaraju, T., Banothu, V., Gundla, K., Addepally, U., & Chimakurthy, J. (2018). Quinazolin derivatives as emerging alpha-glucosidase inhibitors. European Journal of Chemistry, 9(4), 322-330. doi:10.5155/eurjchem.9.4.322-330.1748
Ankireddy, Ashok, Rambabu Gundla, Tuniki Balaraju, Venkanna Banothu, Krishna Prasad Gundla, Uma Addepally, & Jithendra Chimakurthy. "Quinazolin derivatives as emerging alpha-glucosidase inhibitors." European Journal of Chemistry [Online], 9.4 (2018): 322-330. Web. 22 Sep. 2019
Ankireddy, Ashok, Gundla, Rambabu, Balaraju, Tuniki, Banothu, Venkanna, Gundla, Krishna, Addepally, Uma, AND Chimakurthy, Jithendra. "Quinazolin derivatives as emerging alpha-glucosidase inhibitors" European Journal of Chemistry [Online], Volume 9 Number 4 (31 December 2018)

DOI Link: https://doi.org/10.5155/eurjchem.9.4.322-330.1748

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