Synthesis, antimicrobial, and anti-inflammatory activities of novel 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles and 2-(1-adamantylamino)-5-substituted-1,3,4-thiadiazoles.
Reaction of 1-adamantanecarbonyl chloride with certain carboxylic acid hydrazides in pyridine yielded the corresponding N-acyl adamantane-1-carbohydrazide derivatives 3a-j, which were cyclized to the corresponding 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles 4a-j via heating with phosphorus oxychloride. Treatment of 1-adamantylisothiocyanate with some carboxylic acid hydrazides in ethanol yielded the corresponding 1-acyl-4-(1-adamantyl)-3-thiosemicarbazides 7a-g, which were cyclized to the corresponding 2-(1-adamantylamino)-5-substituted-1,3,4-thiadiazole derivatives 8a-g. Compounds 4a-j, 7a-g, and 8a-g were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Several derivatives produced good or moderate activities particularly against the tested Gram-positive bacteria Bacillus subtilis. Meanwhile, compounds 4i and 8g displayed marked antifungal activity against C. albicans. In addition, the in vivo anti-inflammatory activity of the synthesized compounds was determined using the carrageenin-induced paw oedema method in rats. The oxadiazole derivatives 4c, 4g, 4i and 4j produced good dose-dependent anti-inflammatory activity.
Kadi
Adnan A
AA
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
El-Brollosy
Nasser R
NR
Al-Deeb
Omar A
OA
Habib
Elsayed E
EE
Ibrahim
Tarek M
TM
El-Emam
Ali A
AA
D000218:Adamantane / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D015169:Colony Count, Microbial; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008297:Male; D008826:Microbial Sensitivity Tests; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000935:Antifungal Agents; D010069:Oxadiazoles; D013830:Thiadiazoles; D000218:Adamantane