Structure–activity relationship and in silico study of unique bi-heterocycles: 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazole-2-thiol derivatives

Main Article Content

Muhammad Athar Abbasi
Muhammad Shahid Ramzan
Aziz Ur Rehman
Sabhat Zahra Siddiqui
Mubashir Hassan
Hussain Raza
Syed Adnan Ali Shah
Bushra Mirza
Sung-Yum Seo

Abstract

This paper presents the synthesis of some unique bi-heterocyclic hyb­rid molecules with a thiazole and an oxadiazole ring. The synthesis was ini­tiated by the conversion of ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate (1) to the corres­pond­ing 2-(2-amino-1,3-thiazol-4-yl)acetohydrazide (2) by the reaction with hydra­zine hydrate in methanol. The treatment of the acid hydrazide, 2, with carbon disulfide gave the bi-heterocyclic nucleophile, 5-[(2-amino-1,3-
-thiazol-4-yl)­methyl]-1,3,4-oxadiazole-2-thiol (3). Finally, the target com­pounds, 5ao, were synthesized by stirring the nucleophile 3 with different electrophiles, 4ao, in DMF using LiH as a base and an activator. The struc­tures of the newly syn­thesized molecules were confirmed through spectro­scopic techniques, such as IR, EI-MS, 1H-NMR and 13C-NMR. The structure–
–activity relationship of all these bi-heterocycles was established by evaluating them against four enzymes, namely, acetylcholinesterase, butyrylcholines­ter­ase, urease and a-glucosidase, followed by their in silico study. Moreover, their cytotoxicity was also profiled by killing data of brine shrimps at various concentrations.

Article Details

How to Cite
[1]
M. A. Abbasi, “Structure–activity relationship and in silico study of unique bi-heterocycles: 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazole-2-thiol derivatives”, J. Serb. Chem. Soc., vol. 84, no. 7, pp. 649–661, Jul. 2019.
Section
Organic Chemistry
Author Biographies

Muhammad Athar Abbasi, Department of Chemistry, Government College University, Lahore-54000 and College of Natural Sciences, Department of Biological Sciences, Kongju National University, Gongju, 32588 South Korea

Associate Professor

Muhammad Shahid Ramzan, Department of Chemistry, Government College University, Lahore-54000

PhD Scholar, Department of Chemistry,

Aziz Ur Rehman, Department of Chemistry, Government College University, Lahore-54000

Government College University, Lahore-54000

Hussain Raza, College of Natural Sciences, Department of Biological Sciences, Kongju National University, Gongju, 32588

Assiatant Professor

References

A. Foroumadi, S. Mansouri, Z. Kiani, A. Rahmani, Eur. J. Med. Chem. 38 (2003) 851

J. M. Yatin, M. I. Arun, M. Shridhar, I. Shrikrishna, F. Hoong-Kun, Arab. J. Chem. 6 (2013) 177

P. Navin, H. K. Imran, J. Enz. Inhib. Med. Chem. 26 (2011) 527

G. Cihan-Ustundag, B. Simsek, E. Ilhan, G. Capan, Lett. Drug Design Disc. 11 (2014) 290

S. Holla, B. Veerendra, M. K. Shivananda, B. Poojary, Eur. J. Med Chem. 38 (2003) 759

F. Abdel-Rahman, D. C. Erik, H. El-Kashef, Arkivoc 12 (2006) 137

N. Siddiqui, M. F. Arshad, W. Ahsan, M. S. Alam, Int. J. Pharm. Sci. Drug Res. (2009) 143

S. Sanchit, S. N. Pandeya, Int. J. Res. Ayurv. Pharm. 2 (2011) 468

Nagaraj, K. C. Chaluvaraju, M. S. Niranjan, S. Kiran, Int. J. Pharm. Pharm. Sci. 9 (2012) 16

V. Tougu, Curr. Med. Chem. 1 (2001) 155

S. Gauthier, Drug Aging 18 (2001) 853

M. A. Lodhi, M. A. Abbasi, M. I. Choudhary, V. U. Ahmad, Nat. Prod. Res. 21 (2007) 721

M. A. Lodhi, J. Hussain, M. A. Abbasi, A. R. Jassbi, M. I. Choudhary, J. Enz. Inhib. Med. Chem. 21 (2006) 531

H. E. Lebovitz, Clin. North. Am. 26 (1997) 539

G. S. Meneilly, E. A. Ryan, J. Radziuk, D. C. Lau, J. F. Yale, J. Morais, Diabetes care 23 (2000) 1162

M. Nazir, M. A. Abbasi, Aziz-ur-Rehman, S. Z. Siddiqui, K. M. Khan, Kanwal, U. Salar, M. Shahid, M. Ashraf, M. A. Lodhi, F. A. Khan, Bioorg. Chem. 81 (2018), 253

B. Kitchen, H. Decornez, J. R. Furr, J. Bajorath, Nat. Rev. Drug Discov. 3 (2004) 935

M. A. Abbasi, H. Raza, Aziz-ur-Rehman, S. Z. Siddiqui, S. A. A. Shah, M. Hassan, S. Y. Seo. Bioorg. Chem. 83 (2019) 63

K. Rubab, M. A. Abbasi, Aziz-ur-Rehman, S. Z. Siddiqui, and M. N. Akhtar, Trop. J. Pharm. Res. 15 (2016) 1515

G. L. Ellman, K. D. Courtney, V. Andres, R. M. Featherstone, Bio. Pharm. 7 (1961) 88

H. L. Mobley, M. J. Cortesia, L. E. Rosenthal, B. D. Jones, J. Clin. Microbiol. 26 (1988) 831

C. Pierre, R. Roland, J. Y. Dube. Chem. 24 (1978) 208

V. Modi, P. Modi, J. Saud. Chem. Soc. 16 (2012) 332

N. Ullah, G. Bibi, S. Kanwal, Phytochem. Anal. 11 (2012) 241

M. A. Abbasi, M. Hassan, Aziz-ur-Rehman, S. Z. Siddiqui, H. Raza, S. A. A. Shah, S. Y. Seo, Bioorg. Med. Chem. 26 (2018) 3791

M. Nazir, M. A. Abbasi, Aziz-ur-Rehman, S. Z. Siddiqui, H. Raza, M. Hassan, S. A. A. Shah, M. Shahid, S. Y. Seo, RSC Adv. 8 (2018) 25920

M. A. Abbasi, H. Raza, A. U. Rehman, S. Z. Siddiqui, M. Nazir, A. Mumtaz, S. A. A. Shah, S. Y. Seo, M. Hassan, Drug Res (Stuttg.), 2018, doi: 10.1055/a-0654-5074

Q. Abbas, M. Hassan, H. Raza, S. J. Kim, K. W. Chung, G. H. Kim, S. Y. Seo, Asian Pac. J. Trop. Med. 10 (2017) 372

R. Farid, T. Day, R. A. Friesner. Bioorg. Med. Chem. 14 (2006) 3160

M. A. Abbasi, A. Akhtar, Aziz-ur-Rehman, K. Nafeesa, S. Z. Siddiqui, K. M. Khan, M. Ashraf, and S.A. Ejaz, J. Chil. Chem. Soc. 58 (2013) 2186

M. Hassan, S. Shahzadi, S. Y. Seo, H. Alashwal, N. Zaki, A. A. Moustafa. Front. Comput. Neurosci. 12 (2018) 34

M. Hassan, Q. Abbas, Z. Ashraf, A. A. Moustafa, S. Y. Seo, Comput. Biol. Chem. 68 (2017) 131

M. Hassan, Z. Ashraf, Q. Abbas, H. Raza, S. Y. Seo, Interdiscip. Sci. 10 (2018) 68

M. Hassan, S. Shahzadi, Z. Iqbal, JSM Biochem. Mol. Biol. 4 (2017) 1024

M. A. Abbasi, M. Hassan, Aziz-ur-Rehman, S.Z. Siddiqui, S. A. A. Shah, H. Raza, S. Y. Seo, Peer J. 6 (2018) e4962.