2. Academic Validation
  3. Targeted potent antimicrobial benzochromene-based analogues: Synthesis, computational studies, and inhibitory effect against 14α-Demethylase and DNA Gyrase

Targeted potent antimicrobial benzochromene-based analogues: Synthesis, computational studies, and inhibitory effect against 14α-Demethylase and DNA Gyrase

  • Bioorg Chem. 2020 Dec;105:104387. doi: 10.1016/j.bioorg.2020.104387.
Ahmed M Fouda 1,  Ahmed H Hassan 2,  Essam M Eliwa 3,  Hany E A Ahmed 4,  Al-Anood M Al-Dies 5,  Abdelsattar M Omar 6,  Hesham S Nassar 7,  Ahmed H Halawa 3,  Naif Aljuhani 8,  Ahmed M El-Agrody 9
Affiliations

Affiliations

  • 1 Chemistry Department, Faculty of Science, King Khalid University, Abha 61413, Saudi Arabia.
  • 2 Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City 11884, Cairo, Egypt; Chemistry Department, Faculty of Science, Jazan University, Jazan, Saudi Arabia.
  • 3 Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City 11884, Cairo, Egypt.
  • 4 Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah 41477, Saudi Arabia; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, 11884 Nasr City, Cairo, Egypt.
  • 5 Biology and Chemistry Department, Al-Qunfudah University College, Umm Al-Qura University, Al-Qunfudah 1109, Saudi Arabia.
  • 6 Pharmaceutical Chemistry Department, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, 11884 Nasr City, Cairo, Egypt.
  • 7 Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City 11884, Cairo, Egypt; Chemistry Department, Faculty of Science and Art, Al-Baha University, Al-Baha 1988, Saudi Arabia.
  • 8 Pharmacology and Toxicology Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah 41477, Saudi Arabia.
  • 9 Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City 11884, Cairo, Egypt. Electronic address: [email protected].
PMID: 33130344 DOI: 10.1016/j.bioorg.2020.104387
Abstract

7H-Benzo[7,8]chromeno[2,3-d]pyrimidin-9(8H)-amine (6a,b) have been synthesized via hydrazinolysis of the imidates (5a,b). Polysubstituted chromenotriazolopyrimidine (7a-j), (12a,b) and Schiff base (8a,b) derivatives have also been prepared. The new heterocyclic derivatives were affirmed by spectral data. The target compounds have been screened for Antibacterial and Antifungal activity. Compounds 6a,b and 7a-c, g,h displayed the most favorable antimicrobial activities in resemblance to the reference antimicrobial agents by IZ range over 24 mm. In addition, MIC, MBC and MFC were also tested and screen for most active compound 6a by 6.25 µg/mL showing bactericidal effect. SAR study revealed that the antimicrobial vitality of the target compounds was safely influenced by the lipophilicity substituents and the calculated log P value. The potent compounds were subjected into in vitro Enzyme screening (14α-Demethylase and DNA Gyrase) against both interesting targets and showed good inhibitory profile. Molecular modeling analyses were introduced and discussed focusing on the docking of active compounds into two essential targets, and their ADMET properties were studied.

Keywords

14α-Demethylase; ADMET properties; Antimicrobial activities; DNA Gyrase; Molecular modeling; SAR; Triazolopyrimidine.

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