Synthesis, PASS-Predication and in Vitro Antimicrobial Activity of Benzyl 4-O-benzoyl-α-l-rhamnopyranoside Derivatives.
Benzyl α-l-rhamnopyranoside 4, obtained by both conventional and microwave assisted glycosidation techniques, was subjected to 2,3-O-isopropylidene protection to yield compound 5 which on benzoylation and subsequent deprotection of isopropylidene group gave the desired 4-O-benzoylrhamnopyranoside 7 in reasonable yield. Di-O-acetyl derivative of benzoate 7 was prepared to get newer rhamnopyranoside. The structure activity relationship (SAR) of the designed compounds was performed along with the prediction of activity spectra for substances (PASS) training set. Experimental studies based on antimicrobial activities verified the predictions obtained by the PASS software. Protected rhamnopyranosides 5 and 6 exhibited slight distortion from regular ¹C₄ conformation, probably due to the fusion of pyranose and isopropylidene ring. Synthesized rhamnopyranosides 4-8 were employed as test chemicals for in vitro antimicrobial evaluation against eight human pathogenic bacteria and two fungi. Antimicrobial and SAR study showed that the rhamnopyranosides were prone against fungal organisms as compared to that of the bacterial pathogens. Interestingly, PASS prediction of the rhamnopyranoside derivatives 4-8 were 0.49 < Pa < 0.60 (where Pa is probability 'to be active') as antibacterial and 0.65 < Pa < 0.73 as antifungal activities, which showed significant agreement with experimental data, suggesting rhamnopyranoside derivatives 4-8 were more active against pathogenic fungi as compared to human pathogenic bacteria thus, there is a more than 50% chance that the rhamnopyranoside derivative structures 4-8 have not been reported with antimicrobial activity, making it a possible valuable lead compound.
Organic Research Laboratory, Department of Chemistry, University of Chittagong, Chittagong 4331, Bangladesh. mahbubchem@cu.ac.bd.
Mohammed Mahbubul
MM
Matin
Nanotechnology & Catalysis Research Centre (NANOCAT), University of Malaya, Block 3A, Institute of Postgraduate Studies Building, Kuala Lumpur 50603, Malaysia. amit_cu.chem@yahoo.com.
Amit R
AR
Nath
Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia. omar79@siswa.um.edu.my.
Omar
O
Saad
Organic Research Laboratory, Department of Chemistry, University of Chittagong, Chittagong 4331, Bangladesh. mosharefchem@cu.ac.bd.
Mohammad M H
MM
Bhuiyan
Division of Human Biology, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia. faalhadi@yahoo.com.
Farkaad A
FA
Kadir
Nanotechnology & Catalysis Research Centre (NANOCAT), University of Malaya, Block 3A, Institute of Postgraduate Studies Building, Kuala Lumpur 50603, Malaysia. sharifahbee@um.edu.my.
Sharifah Bee
SB
Abd Hamid
Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia. aaalhamadani@yahoo.com.
Abeer A
AA
Alhadi
Nanotechnology & Catalysis Research Centre (NANOCAT), University of Malaya, Block 3A, Institute of Postgraduate Studies Building, Kuala Lumpur 50603, Malaysia. eaqubali@um.edu.my.
Md Eaqub
ME
Ali
Nanotechnology & Catalysis Research Centre (NANOCAT), University of Malaya, Block 3A, Institute of Postgraduate Studies Building, Kuala Lumpur 50603, Malaysia. wdabdoub@um.edu.my.
Wageeh A
WA
Yehye
D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002240:Carbohydrate Sequence; D005658:Fungi / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009844:Oligosaccharides / Q000737:chemistry*; D012210:Rhamnose / Q000737:chemistry*; D012984:Software; D013329:Structure-Activity Relationship
D000890:Anti-Infective Agents; D009844:Oligosaccharides; D012210:Rhamnose
L-rhamnose; antimicrobial agents; benzoylation; benzyl α-L-rhamnopyranoside; prediction of activity spectra for substances (PASS); structure activity relationship