In silico and In vitro Antitubercular Studies for Nitrogen Rich Hybrids of homopiperazine-pyrimidine-Pyrazole Adducts

Bhavinkumar Vavaiya; Shivani Patel; Vrajlal Pansuriya; Vanita Marvaniya; Popatbhai Patel

doi:10.14233/ajchem.2022.23520

Issue

Vol. 34 No. 3 (2022): Vol 34 Issue 3, 2022

Issue Published : February 14, 2022

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

In silico and In vitro Antitubercular Studies for Nitrogen Rich Hybrids of homopiperazine-pyrimidine-Pyrazole Adducts

https://doi.org/10.14233/ajchem.2022.23520

Bhavinkumar Vavaiya

Department of Chemistry, M.G. Science Institute, Navrangpura, Ahmedabad-380009, India

Shivani Patel

Biological and Life Sciences, School of Arts and Sciences, Ahmedabad University, Navrangpura, Ahmedabad-380009, India

Vrajlal Pansuriya

Department of Chemistry, School of Science, Gujarat University, Ahmedabad-380009, India

Vanita Marvaniya

Shree Swaminarayan Sanskar Pharmacy College, Zundal, Gandhinagar-382421, India

Popatbhai Patel

Department of Chemistry, M.G. Science Institute, Navrangpura, Ahmedabad-380009, India

Corresponding Author(s) : Popatbhai Patel

vavaiyabhavin@gmail.com

Asian Journal of Chemistry, Vol. 34 No. 3 (2022): Vol 34 Issue 3, 2022
Article Published : February 14, 2022

Abstract

Novel homopiperazine-pyrimidine-pyrazole hybrids (3a-j) were synthesized using ethyl 2-cyanoacetate and 4,6-dichloropyrimidine as starting materials by a multi-step process to afford ethyl 5-amino-1-(6-chloropyrimidin-4-yl)-1H-pyrazole-4-carboxylate in good yields using polar protic media. The intermediate 1, in two steps, chloroamine condensation followed by acid amine coupling, furnished the title compounds ethyl 5-amino-1-(6-(4-substituted aryl-1,4-diazepan-1-yl)pyrimidin-4-yl)-1H-pyrazole- 4-carboxylate (3a-j). The synthesized compounds were docked in the crystal structure of Mycobacterium tuberculosis (PDB ID: 4TRO) to get insights into structural requirements for antitubercular activity. In vitro antitubercular activity against M. tuberculosis H37Rv strains showed that compounds 3a, 3d, 3e and 3g were found to be the most potent (Docking score: > -21; MIC = 1.6 μg/mL) among the synthesized molecules. All the synthesized compounds showed acceptable drug-like properties which make them suitable for further lead modification using in silico design approaches.

Keywords

Pyrazole Pyrazole Pyrimidine Pyrimidine Homopiperazine Homopiperazine Molecular docking Molecular docking Antitubercular activity Antitubercular activity

Vavaiya, B., Patel, S., Pansuriya, V., Marvaniya, V., & Patel, P. (2022). In silico and In vitro Antitubercular Studies for Nitrogen Rich Hybrids of homopiperazine-pyrimidine-Pyrazole Adducts. Asian Journal of Chemistry, 34(3), 562–568. https://doi.org/10.14233/ajchem.2022.23520

Download Citation

References

E. Cambau and M. Drancourt, Clin. Microbiol. Infect., 20, 196 (2014); https://doi.org/10.1111/1469-0691.12555
S. Luca and T. Mihaescu, Maedica (Buchar.), 8, 53 (2013).
I. Barberis, N. Bragazzi, L. Galluzzo and M. Martini, J. Prev. Med. Hyg., 58, E9 (2017).
F. Dalberto, V. de Souza, L. Abbadi, E. Christiano, S. Raoní, S. Alessandro, S. Fernanda and M. Pablo, Front Chem., 8, 984 (2020); https://doi.org/10.3389/fchem.2020.586294
J. Jampilek, Molecules, 24, 3839 (2019); https://doi.org/10.3390/molecules24213839
A. Trivedi, B. Dholariya, C. Vakhariya, D. Dodiya, H. Ram, V. Kataria, A. Siddiqui and V. Shah, Med. Chem. Res., 21, 1887 (2012); https://doi.org/10.1007/s00044-011-9712-3
F. Chaudhry, S. Naureen, M. Ashraf, M. Al-Rashida, B. Jahan, M. Munawar and M. Khan, Bioorg. Chem., 82, 267 (2019); https://doi.org/10.1016/j.bioorg.2018.10.047
A. Vijesh, A. Isloor, S. Telkar and S. Peethambar, Eur. J. Med. Chem., 46, 3531 (2011); https://doi.org/10.1016/j.ejmech.2011.05.005
G. Menozzi, L. Merello, P. Fossa, S. Schenone, A. Ranise, L. Mosti, F. Bondavalli and R. Loddo, Bioorg. Med. Chem., 12, 5465 (2004); https://doi.org/10.1016/j.bmc.2004.07.029.
D. Ashok, M. Reddy, N. Nagaraju, R. Dharavath, K. Ramakrishna, S. Gundu, P. Shravani and M. Sarasija, Med. Chem. Res., 29, 699 (2020); https://doi.org/10.1007/s00044-02002515-6
C. Dumontet and M. Jordan, Nat. Rev. Drug Discov., 9, 790 (2010); https://doi.org/10.1038/nrd3253
Y. Duan, Y. Sang, J. Makawana, S. Teraiya, Y. Yao, D. Tang, X. Tao and H. Zhu, Eur. J. Med. Chem., 85, 341 (2014); https://doi.org/10.1016/j.ejmech.2015.05.021
X. Zhang, S. Raghavan, M. Ihnat, J. Thorpe, A. Bastian, L. Bailey-Downs, B. Disch, N. Dybdal Hargreaves, C. Rohena, E. Hamel, S. Mooberry and A. Gangjee, Bioorg. Med. Chem., 22, 3753 (2014); https://doi.org/10.1016/j.bmc.2015.03.061
F. Xie, H. Zhao and L. Zhao, Bioorg. Med. Chem. Lett., 19, 275 (2009); https://doi.org/10.1016/j.bmcl.2008.09.067
J.W. Shao, Y.C. Dai, J.P. Xue, J.C. Wang, F.P. Lin and Y.H. Guo, Eur. J. Med. Chem., 46, 2652 (2011); https://doi.org/10.1016/j.ejmech.2011.03.050
J. Lassen, N. Holm, G. Stankovic, T. Lefèvre, A. Chieffo, D. HildickSmith, M. Pan, O. Darremont, R. Albiero, M. Ferenc and Y. Louvard, EuroIntervention, 10, 545 (2014); https://doi.org/10.4244/eij d-17-00622
A. Mekky and S. Sanad, Bioorg. Chem., 102, 104094 (2020); https://doi.org/10.1016/j.bioorg.2020.104094
K. Thriveni, B. Padmashali, M. Siddesh and C. Sandeep, Indian J. Pharm. Sci., 76, 332 (2014).

References

E. Cambau and M. Drancourt, Clin. Microbiol. Infect., 20, 196 (2014); https://doi.org/10.1111/1469-0691.12555

S. Luca and T. Mihaescu, Maedica (Buchar.), 8, 53 (2013).

I. Barberis, N. Bragazzi, L. Galluzzo and M. Martini, J. Prev. Med. Hyg., 58, E9 (2017).

F. Dalberto, V. de Souza, L. Abbadi, E. Christiano, S. Raoní, S. Alessandro, S. Fernanda and M. Pablo, Front Chem., 8, 984 (2020); https://doi.org/10.3389/fchem.2020.586294

J. Jampilek, Molecules, 24, 3839 (2019); https://doi.org/10.3390/molecules24213839

A. Trivedi, B. Dholariya, C. Vakhariya, D. Dodiya, H. Ram, V. Kataria, A. Siddiqui and V. Shah, Med. Chem. Res., 21, 1887 (2012); https://doi.org/10.1007/s00044-011-9712-3

F. Chaudhry, S. Naureen, M. Ashraf, M. Al-Rashida, B. Jahan, M. Munawar and M. Khan, Bioorg. Chem., 82, 267 (2019); https://doi.org/10.1016/j.bioorg.2018.10.047

A. Vijesh, A. Isloor, S. Telkar and S. Peethambar, Eur. J. Med. Chem., 46, 3531 (2011); https://doi.org/10.1016/j.ejmech.2011.05.005

G. Menozzi, L. Merello, P. Fossa, S. Schenone, A. Ranise, L. Mosti, F. Bondavalli and R. Loddo, Bioorg. Med. Chem., 12, 5465 (2004); https://doi.org/10.1016/j.bmc.2004.07.029.

D. Ashok, M. Reddy, N. Nagaraju, R. Dharavath, K. Ramakrishna, S. Gundu, P. Shravani and M. Sarasija, Med. Chem. Res., 29, 699 (2020); https://doi.org/10.1007/s00044-02002515-6

C. Dumontet and M. Jordan, Nat. Rev. Drug Discov., 9, 790 (2010); https://doi.org/10.1038/nrd3253

Y. Duan, Y. Sang, J. Makawana, S. Teraiya, Y. Yao, D. Tang, X. Tao and H. Zhu, Eur. J. Med. Chem., 85, 341 (2014); https://doi.org/10.1016/j.ejmech.2015.05.021

X. Zhang, S. Raghavan, M. Ihnat, J. Thorpe, A. Bastian, L. Bailey-Downs, B. Disch, N. Dybdal Hargreaves, C. Rohena, E. Hamel, S. Mooberry and A. Gangjee, Bioorg. Med. Chem., 22, 3753 (2014); https://doi.org/10.1016/j.bmc.2015.03.061

F. Xie, H. Zhao and L. Zhao, Bioorg. Med. Chem. Lett., 19, 275 (2009); https://doi.org/10.1016/j.bmcl.2008.09.067

J.W. Shao, Y.C. Dai, J.P. Xue, J.C. Wang, F.P. Lin and Y.H. Guo, Eur. J. Med. Chem., 46, 2652 (2011); https://doi.org/10.1016/j.ejmech.2011.03.050

J. Lassen, N. Holm, G. Stankovic, T. Lefèvre, A. Chieffo, D. HildickSmith, M. Pan, O. Darremont, R. Albiero, M. Ferenc and Y. Louvard, EuroIntervention, 10, 545 (2014); https://doi.org/10.4244/eij d-17-00622

A. Mekky and S. Sanad, Bioorg. Chem., 102, 104094 (2020); https://doi.org/10.1016/j.bioorg.2020.104094

K. Thriveni, B. Padmashali, M. Siddesh and C. Sandeep, Indian J. Pharm. Sci., 76, 332 (2014).

Issue

Vol. 34 No. 3 (2022): Vol 34 Issue 3, 2022

In silico and In vitro Antitubercular Studies for Nitrogen Rich Hybrids of homopiperazine-pyrimidine-Pyrazole Adducts

Corresponding Author(s) : Popatbhai Patel

Abstract

Keywords

Full Article

Download Citation

References

Table Of Contents