First example of Azo-Sulfa conjugated chromene moieties: Synthesis, characterization, antimicrobial assessment, docking simulation as potent class I histone deacetylase inhibitors and antitumor agents

Rawda M Okasha; Mosa Alsehli; Saleh Ihmaid; Sultan S Althagfan; Mohamed S A El-Gaby; Hany E A Ahmed; Tarek H Afifi

doi:10.1016/j.bioorg.2019.103262

First example of Azo-Sulfa conjugated chromene moieties: Synthesis, characterization, antimicrobial assessment, docking simulation as potent class I histone deacetylase inhibitors and antitumor agents

Bioorg Chem. 2019 Nov:92:103262. doi: 10.1016/j.bioorg.2019.103262. Epub 2019 Sep 5.

Authors

Rawda M Okasha¹, Mosa Alsehli¹, Saleh Ihmaid², Sultan S Althagfan³, Mohamed S A El-Gaby⁴, Hany E A Ahmed⁵, Tarek H Afifi⁶

Affiliations

¹ Chemistry Department, Faculty of Science, Taibah University, 30002, Al-Madinah Al-Munawarah, Saudi Arabia.
² Pharmacognosy and Pharmaceutical Chemistry Department, Pharmacy College, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia.
³ Clinical and Hospital Pharmacy Department, Taibah University, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah 41477, Saudi Arabia.
⁴ Department of Chemistry, Faculty of Science, Al-Azhar University at Assiut, Assiut 71524, Egypt.
⁵ Pharmacognosy and Pharmaceutical Chemistry Department, Pharmacy College, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, 11884 Nasr City, Cairo, Egypt.
⁶ Chemistry Department, Faculty of Science, Taibah University, 30002, Al-Madinah Al-Munawarah, Saudi Arabia; Chemistry Department, Faculty of Science, Al-Azhar University, 11884 Nasr City, Cairo, Egypt. Electronic address: afifith@yahoo.com.

PMID: 31518757
DOI: 10.1016/j.bioorg.2019.103262

Abstract

This report presents the development of a novel and primary model of sulfonamide compounds encompassing a chromene azo motif with the intent of becoming applicable for drug candidates in the cases of drug-resistant pathogens. The novel molecules (7a-n) have been synthesized via a two-step reaction. First, 4-((2, 4-dihydroxyphenyl)diazenyl)benzenesulfonamide (3a-e) were obtained through the reaction of their corresponding diazotized 4-aminobenzenesulfonamides (1a-e) with resorcinol, followed by the heterocyclization of 3a-e with arylidenemalononitriles (6a-d). Upon structural identification, the newly synthesized compounds were evaluated for their antibacterial and antifungal activities. Moreover, their cytotoxic screening was performed against three cancer cell lines: HCT-116, HepG-2, and MCF-7. Further examinations were comprised of the inhibitory effect analyses of the novel sulfonamide/chromene derivatives against the HDAC classes and the Tubulin polymerization in order to discern the prime antitumor drug candidates.

Keywords: Anticancer activity; Antimicrobial; Chromene; HDAC examination; Sulfonamide.

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Azo Compounds / chemistry
Azo Compounds / pharmacology*
Benzopyrans / chemistry
Benzopyrans / pharmacology*
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Histone Deacetylase 1 / antagonists & inhibitors
Histone Deacetylase 1 / metabolism
Histone Deacetylase 2 / antagonists & inhibitors
Histone Deacetylase 2 / metabolism
Histone Deacetylase Inhibitors / chemical synthesis
Histone Deacetylase Inhibitors / chemistry
Histone Deacetylase Inhibitors / pharmacology*
Histone Deacetylases / metabolism
Humans
Molecular Docking Simulation*
Molecular Structure
Repressor Proteins / antagonists & inhibitors
Repressor Proteins / metabolism
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Antineoplastic Agents
Azo Compounds
Benzopyrans
Histone Deacetylase Inhibitors
Repressor Proteins
HDAC1 protein, human
HDAC2 protein, human
HDAC8 protein, human
Histone Deacetylase 1
Histone Deacetylase 2
Histone Deacetylases