Contents lists available at ScienceDirect Bioorganic & Medicinal Chemistry Letters journal homepage: www.elsevier.com/locate/bmcl Sulfamic acid catalyzed synthesis of new 3,5-[(sub)phenyl]-1H-pyrazole bearing N 1 -isonicotinoyl: And their pharmacological activity evaluation Jayashri D. Bhirud a, ⁎ , Rajendra D. Patil a, ⁎ , Hemant P. Narkhede b a School of Chemical Sciences, Moolji Jaitha College, Jalgaon (An Autonomous College Affiliated to K.B.C. N. M. U. University, Jalgaon), Maharshtra 425002, India b Smt. P. K. Kotecha Mahila Mahavidyalaya, Bhusawal, Dist-Jalgaon, Maharashtra 425305, India ARTICLE INFO Keywords: Sulfamic acid 3,5-[(Sub)phenyl]-1H-pyrazole Anti-oxidant Anti-mycobacterial Anti-cancer ABSTRACT A sustainable synthesis of new 3,5-[(sub)phenyl]-1H-pyrazole bearing N 1 -isonicotinoyl derivatives from sub- stituted chalcones and isoniazid by using sulfamic acid and their pharmacological activity evaluation is reported. An anti-oxidant study is performed by using DPPH assay. In vitro anti-mycobacterial activity of compounds bearing R/R′ = 4-CH 3 /4-F and 3-OCH 3 /4-Cl showed complete inhibition (99%) at the MIC of 31 and 34 μM respectively. Antibacterial screening of compounds bearing R/R′ = 4-CH 3 /4-F; 4-OCH 3 /4-Br; and 4-OCH 3 /4-Cl has shown noticeable inhibition (27 mm) against Staphylococcus aureus. The anti-cancer bioassay demonstrated that the five compounds were active on human breast cancer cell line MCF-7; however on HeLa cervical cancer cells only two compounds are active in comparison to standard drug Doxorubicin. Higher inhibitory effects observed in this study appear to be dependent on the chloro, bromo, fluoro and methoxy functionality present on the aromatic nucleus. The structures of all the compounds are established using NMR ( 1 H and 13 C), FT-IR, Mass and elemental analysis. The pyrazole moieties are highly important pharmacologically ac- tive organic compounds found in medicinally active substances. They are well known for their wide range of pharmacological activities such as anti-cancer, anti-viral, anti-oxidant, anti-microbial, anti-pyretic, anti- diabetic, anti-inflammatory, anti-convulsant, anti-psychotic, anti-obe- sity, a H2-receptor agonist, anti-depressant, analgesic etc. 1 Numerous synthetic routes have been reported for the development of pyrazole hybrid scaffolds. Moreover, pyrazole scaffolds interesting structures and potential pharmacological activities still attracting the attention of researchers to synthesize novel scaffolds. In continuation of our on- going research in this field, 2 we have undertaken the present in- vestigation to develop new 3,5-[(sub)phenyl]-1H-pyrazolebearing N 1 - isonicotinoyl and to explore their anti-oxidant, anti-bacterial, anti- mycobacterial and anti-cancer activities. Substituted pyrazole derivatives have been synthesized from chal- cones using hydrazine, substituted hydrazines, and hydrazides. 1 Synthesis of 1,3,5-trisubstituted pyrazole(s) having one of the N-atom substituted with biologically active moieties such as acylamide, aryl/ sulfonyl, benzene sulfonamide etc. are reported. 3 A series of 1,3,5-tri- substituted pyrazoline(s) bearing N 1 -isonicotinoyl were synthesized from chalcones and hydrazides using catalytic glacial acetic acid 4 and pyridine. 5 Recently a rapid synthesis of similar pyrazoline derivatives from chalcones were reported with microwave radiations 6 and ultrasonification. 7 The above reported methods for the synthesis of 2,5- dihydro-1H-pyrazole bearing N 1 -isonicotinoyl uses homogenous glacial acetic acid and pyridine as catalysts. These homogenous catalysts have good solubility in reaction solvents and are not convenient to recover and reuse. The use of microwave and ultrasonification for activation of the reactants is demonstrated. In view of these aspects, the develop- ment of efficient and milder methods for the synthesis of these scaffolds is of considerable interest. We herein report a simple, economical and sustainable method for the synthesis of 1,3,5-trisubstituted pyrazole(s) bearing isonicotinoyl group by using sulfamic acid (H 2 NSO 3 H) as catalyst. Sulfamic acid has been used as an efficient heterogeneous catalyst for acid-catalyzed re- actions. Sulfamic acid is a stable, inexpensive, non-corrosive, non-hy- groscopic, non-volatile and highly efficient as well as a greener cata- lyst. 8 This catalyst could be easily recycled and reused due to its very high immiscibility with most organic solvents and miscibility in water. It has been used as a solid acid catalyst for many important heterocyclic synthesis such as phenanthrene fused-dihydrodibenzo-quinolinones, spirooxindoles, 1,2-dihydroquinazoline, N-phenylpyrazole, 2,4,5-triar- ylimidazoles and 2-arylphenanthrimidazoles etc. 8,9 To the best of our knowledge this is the first report for the sulfamic acid catalyzed synthesis of 3,5-[(sub)phenyl]-1H-pyrazole bearing N 1 -isonicotinoyl from chalcones. https://doi.org/10.1016/j.bmcl.2020.127558 Received 12 June 2020; Received in revised form 6 September 2020; Accepted 13 September 2020 ⁎ Corresponding authors. E-mail addresses: ingale.jayashri@rediffmail.com (J.D. Bhirud), r_dpatil123@yahoo.co.in (R.D. Patil). Bioorganic & Medicinal Chemistry Letters 30 (2020) 127558 Available online 19 September 2020 0960-894X/ © 2020 Elsevier Ltd. All rights reserved. T