2. Academic Validation
  3. Diastereomeric pure pyrazolyl-indolyl dihydrofurans: Unveiling isomeric selectivity in antibacterial action via in vitro and in silico insights

Diastereomeric pure pyrazolyl-indolyl dihydrofurans: Unveiling isomeric selectivity in antibacterial action via in vitro and in silico insights

  • Bioorg Med Chem Lett. 2024 Dec 1:114:130005. doi: 10.1016/j.bmcl.2024.130005.
Hari Prakash 1,  Sandhya Chahal 2,  Jayant Sindhu 3,  Prateek Tyagi 4,  Deepansh Sharma 5,  Mridula Guin 6,  Noopur Srivastava 7,  Kuldeep Singh 8
Affiliations

Affiliations

  • 1 Jubilant Biosys Ltd., Knowledge Park-II, Greater Noida 201310, Uttar Pradesh, India; Department of Chemistry, Sharda School of Basic Sciences & Research, Sharda University, Knowledge Park-III, Greater Noida 201310, Uttar Pradesh, India.
  • 2 Department of Chemistry, Chaudhary Ranbir Singh University, Jind, Haryana 126102, India.
  • 3 Department of Chemistry, COBS&H, Chaudhary Charan Singh Haryana Agricultural University, Hisar 125004, India.
  • 4 Department of Chemistry, Zakir Husain Delhi College, New Delhi, Delhi 110002, India.
  • 5 Department of Life Sciences, J.C. Bose University, Science and Technology, YMCA, Faridabad 126001, India.
  • 6 Department of Chemistry, Sharda School of Basic Sciences & Research, Sharda University, Knowledge Park-III, Greater Noida 201310, Uttar Pradesh, India.
  • 7 Department of Chemistry, Sharda School of Basic Sciences & Research, Sharda University, Knowledge Park-III, Greater Noida 201310, Uttar Pradesh, India. Electronic address: noopursriv@gmail.com.
  • 8 Jubilant Biosys Ltd., Knowledge Park-II, Greater Noida 201310, Uttar Pradesh, India. Electronic address: deshwal.chem@gmail.com.
PMID: 39454968 DOI: 10.1016/j.bmcl.2024.130005
Abstract

Developing pure diastereoisomeric molecular hybrids for the selective inhibition of Bacterial growth opened new avenues for combating the ever-increasing microbial resistance. Considering this, a series of diastereoisomeric pure pyrazolyl-dihydrofurans (7a-7y) were synthesized and characterized using NMR, LCMS, and X-ray crystallography. DFT based method was used to explore the configurational stability of cis over trans isomeric form. Considering 7a and 8a as representative isomeric forms with same structural framework, the difference in their bio-efficacy against Bacterial and Fungal strains was assessed using serial dilution method. The relatively high inhibition of Bacterial growth by the cis isomeric form (7a) (MIC = 1.562 µg/mL), amoxicillin (MIC = 3.125 µg/mL) inspired us to broaden the substrate scope for synthesizing a series of pure diastereoisomeric cis forms as selective anti-bacterial agents. However, both the isomers displayed Antifungal activity less than the standard drug (Fluconazole) employed in the study. All the reactions proceeded smoothly and yielded a diverse array of dihydrofuran derivatives. The developed synthetics were found to be non-cytotoxic against mouse fibroblast cells and didn't affect the seed germination of Brassica nigra seeds when treated at 1 mg/mL concentration. The experimentally determined in vitro results were further validated using in silico molecular docking and dynamics studies.

Keywords

Anti-microbial; DFT and in silico study; Diastereoisomeric forms; Dihydrofuran; Indole; Pyrazole.

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