Department of Pharmaceutical Chemistry

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Details of Dr Mohammad Kaisarul Islam


Education:

PhD in Pharmaceutical Chemistry, King’s College London, UK, 2016.
Masters in Pharmaceutical Chemistry, University of Dhaka, Bangladesh, 2006.
B. Pharm (Hons.), University of Dhaka, Bangladesh, 2005.

Research Interest:

Drug design and discovery is an essential area of research in present days because of its influence in medicinal chemistry and human life span. I was trained in medicinal chemistry and drug design (i.e., anticancer drug discovery) during my PhD training with Prof David Thurston of King’s College London. In my Ph. D work, I synthesized and evaluated number of small molecules targeting DNA/RNA hybrid duplexes as an anticancer strategy. This project began by using oligonucleotides representing telomeric DNA/RNA hybrid duplex, telomeric G-quadruplex and control duplex DNA sequences to screen against the National Cancer Institute compound libraries using a high throughput FRET based DNA thermal denaturation assay to determine binding affinity and specificity. Thirteen novel chemical scaffold families were identified in the assay, compounds which showed a >5 °C selective stabilization of the DNA/RNA hybrid duplex at a 1 μM ligand concentration. Chemical modifications were then made to these scaffolds to generate focused libraries of analogues to improve selectivity, potency and drug-likeness, and to provide SAR information. I have gained knowledge in medicinal chemistry and biophysical and biological assays during my PhD studies. To generate different scaffolds of molecule, various single- and multi-step reactions were involved, which allowed me to earn good experience in medicinal chemistry and drug discovery. I have also gained experience in characterisation methods including LC-MS, NMR, UV and IR spectroscopy. I have good hand in FRET melting assay, cytotoxicity assay and moderate skills in RT-PCR and gel electrophoresis. Since, I want to develop my experience in drug discovery, I joined with Dr Daniele Castagnolo’s lab at KCL, as a postdoctoral researcher. During that project, I could develop some novel pyrrol molecules targeting gram-ve bacteria, which is showing considerable attention to the scientific community in recent years due to antibiotic resistance in many cases. Results generated from this project are waiting for some biological data, which afterwards will be published as a full article.

Future Plan-Telomere targeted anticancer drug discovery

Discovering an anticancer drug is one of my long time goal. Telomere and telomerase targeted drug discovery is a broad area of research, which can be selective and most efficient way to kill cancer. Number of published article have claimed about 85% cancer cells are experiencing up-regulation of telomerase, a reverse transcriptase enzyme responsible for elongation of telomeric end of chromosome and help the cancer cell to go for further division. Upregulation of the level hTERT and hTR is linked to human cancer. In contrast to telomerase activity, where an RNA template is used for the synthesis of new telomeric DNA, the alternative lengthening of telomeres (ALT) mechanism involves the elongation of the telomeric DNA sequence from a DNA template via a homologous recombination protein, that ultimately lead to tumour growth.

Anticancer approaches directed at telomerase inhibition can be varied and possible methods include stabilizing telomeric G-quadruplex structures, RNA interference (RNA) of the hTERT catalytic subunit and stabilizing DNA/RNA hybrid duplex structures towards the large protein surface of the telomerase enzyme.

Different research groups are mostly working to stabilize the G-quadruplex structures as an anticancer strategy either in promoter regional quadruplex structure or telomeric quadruplex. However, targeting hTERT, hTR or telomeric DNA/RNA hybrid still remains unexplored. I, personally, did some works on telomeric DNA/RNA hybrid targeted drug design and development during my PhD research. In 1999, Prof. Jonathan B. Chaires and his research group reported some know structures (e.g., ethidium bromide, coralyne chloride and DAPI) with minimal effectivity towards the hybrid. In 2010, Prof. Wheelhouse and his team reported a diaryl substituent and pyrimidine analogue with a greater preference for the hybrid duplex compared to the duplex DNA; however it was not reported for the telomeric DNA/RNA hybrid sequence. In 2001, two naphthalene-type molecules were reported as highly selective telomerase inhibitors, where BIBR1532 showed competitive binding to the active site of hTERT but it did not block the template copying site for the telomere elongation process. PARP inhibitor, Olaparib, has approved by FDA as a targeted therapy of cancers with hereditary BRCA1 or BRCA2 mutations (including ovarian, breast, and prostate cancers), which is acting by inhibiting Tankyrase-1. Thus it is clear that there are not many outcome from this research field, however, it is well know that telomerase is over expressed in every cancer cells and lead to propagation of tumour growth and causes cancer related morbidity.

My future plan is to employ my medicinal chemistry skills and knowledge to design new chemical scaffold to target hTERT and/or hTR expression and thus minimizing the catalytic nactivity of telomerase. Many studies have focused on the role of transcriptional control of hTERT expression or on phosphorylation-induced increases in hTERT activity. Protein kinase Ca and PkB can phosphorylate hTERT. Mutations within the core promoter region of hTERT are common, and these may increase hTERT transcriptional activity by creating new consensus binding motifs for ETS transcription factors. hTERT promoter mutations are most common in malignancies like bladder carcinoma, liposarcomas (e.g., fat cells of deep soft tissue), hepatocellular carcinoma, squamous cell carcinoma (e.g., tongue), medulloblastomas (i.e., malignant primary brain tumour) and glioblastoma (aggressive malignant primary brain tumour). Another mechanism of up-regulation is translocation of the hTERT gene to an immunoglobulin gene or other loci in B-cell neoplasms, which presumably contributes to the increased hTERT transcription and telomerase activity observed in these tumours. The human telomerase catalytic subunit (hTERT) and the RNA template molecule (hTR) are both present in very low amount in normal cells, and it is likely that the expression of both must be increased in order to express sufficient telomerase to prevent telomere shortening in cancer cells. Thus if we can control the expression of hTERT and hTR, cancer cell cycle also could be controlled and forced to apoptosis.

I have expectation to continue to develop on these research streams in the future. I believe my work in drug discovery will provide many prospects for interesting, cutting edge study in the field of medicinal chemistry that is relatively new. I constantly sharpen my skills through updates from literature, seminars and my interactions with faculty and colleague. Furthermore, I hope to advance the traditional drug discovery field with new questions and pertinent issues of twenty-first century.

Research Publications
1. Mohammad K. Islam, Paul J. M. Jackson, Khondaker M. Rahman, David E. Thurston. Recent advances in targeting the telomeric G-quadruplex DNA sequence with small molecules as a strategy for anticancer therapies. Future Med Chem. 8(11), 1259-1290, 2016. DOI: 10.4155/fmc-2015-0017
2. Mia Mohammad Dulal, Md Kaisarul Islam, Abu Asad Chowdhury, Jakir Ahmed Chowdhury. Prevention of cap-locking of syrup product by treating the manufacturing process of sugar syrup with citric acid monohydrate. Bangladesh Pharmaceutical Journal 19(2): 190-196, 2016. DOI: 10.3329/bpj.v19i2.29279
3. Mohammad Kaisarul Islam, Md. Hossain Sohrab and Abdul Jabbar. Caffeine and p-anaisaldehyde from the fruits of Enterolobium saman Prain. Int. J. Pharm. Sci and Res. 3(1). 168-170 (2012). DOI: 10.13040/IJPSR.0975-8232.3(1).168-70
4. Mohammad Kaisarul Islam and Khondaker Ashakin. Antimicrobial screening and brine shrimp lethality bioassay of Tinospora cordifolia (Fam: Menispermeaceae). Int. J. Pharm. Sci and Res. 2(11). 3091-3095 (2011). DOI: 10.13040/IJPSR.0975-8232.2(12).3091-95
5. Md. Mominur Rahman, Jakir Ahmed Chowdhury, Razibul Habib, Barun Kanti Saha, A.D.M Salauddin and Mohammad Kaisarul Islam. Anti-inflammatory, anti-arthritic and analgesic activity of the alcoholic extracts of the plant Urginea indica Kunth. Int. J. Pharm. Sci and Res. 2(9). 2320-2324 (2011). DOI: 10.13040/IJPSR.0975-8232.2(11).2915-19
6. Md Ruhul Amin, Moynul Hasan, Abdullah Al Masud, Md Hanif uddin, Md Hasanuzzaman and Mohammad Kaisarul Islam. Validated UV spectrophotometric method for estimation of Dutasteride in tablet dosage form. Pharmacie Globale: International Journal of Comprehensive Pharmacy (IJCP). 1(4). 1-3 (2011).
7. Abdullah Al Masud, Md. Shamsul Arefeen, Mohammad Kaisarul Islam, Moynul Hasan. Development and validation of a RP-HPLC method for the estimation of Levetiracetam in bulk and pharmaceutical formulation. Journal of Chemical and Pharmaceutical Research. 3(1). 324-329 (2011). ISSN: 0975-7384
8. Al-Mamun R, Hamid A, Islam MK, Chowdhury JA and Zafrul Azam ATM. Lipid lowering activity and free radical scavenging effect of Cinnamomum tamala (Fam: Lauraceae). International Journal of Natural Sciences. 1(4). 93-96 (2011). DOI:10.3329/ijns.v1i4.9735
9. Jakir Ahmed Chowdhury, Sheikh Tasnim Jahan, Md. Masud Morshed, Jewel Mallick, Aninda Kumar Nath, Md Zia Uddin, Mycal Dutta, M. Kaisarul Islam, Md. Hassan Kawsar. Development and evaluation of diclofenac sodium loaded alginate cross-linking beads. Bangladesh Pharmaceutical Journal. 14 (1), 41-48 (2011). ISSN: 0301-4606
10. M. K. Islam, J. A. Chowdhury, I. Z. Eti. Biological Activity study on a Malvaceae plant: Bombax ceiba. Journal of Scientific Research. 3 (2), 445-450 (2011). DOI: http://dx.doi.org/10.3329/jsr.v3i2.5162
11. Mohammad Kaisarul Islam, Qamer Ibn Sharif, Neher Sultana Sherin, Jakir Ahmed Chowdhury. In vitro evaluation of Theophylline SR dosage form available on the Bangladeshi drug market. Journal of Dhaka International University. 2(1). 143-147 (2011).
12. Mohammad Kaisarul Islam, Moynul Hasan, Nasrin Akhter, Jakir Ahmed Chowdhury. Quantitative and qualitative estimation of marketed paracetamol products in Bangladesh: Solid dosage forms. Journal of Dhaka International University. 2(1). 148-153 (2011).
13. M. Kaisarul Islam, Israt Zahan Eti, Jakir Ahmed Chowdhury. Phytochemical and antimicrobial works on Oroxylum indicum Linn. Iranian Journal of Pharmacology and Therapeutic). 9(1). 25-28 (2010). (Online: http://en.journals.sid.ir/ViewPaper.aspx?ID=181098)
14. Mohammad Borhan Uddin, Jakir Ahmed Chowdhury, Kazi Rashidul Azam, M. Kaisarul Islam. Investigation of the effects of different physicochemical parameters on in vitro release kinetics of theophylline from Eudragit NE 30 and Eudragit RS 30D matrix tablets. J. Pharm. Sci. & Res. 2(4). 240-246 (2010). ISSN: 0975-1459 (Online: http://www.jpsr.pharmainfo.in/issue.php?page=8)
15. Rakib Al-Mamun, Abdul Hamid, Mohammad Kaisarul Islam, Jakir Ahmed Chowdhury. Cytotoxic and thrombolytic activity of leaves extract of Parthenium hysterophorus (Fam: Asteraceae). Bangladesh Pharmaceutical Journal. 13 (2), 51-54 (2010). ISSN: 0301-4606
16. Sheikh Tasnim Jahan, Md. Saiful Islam, Sams Mohammad Anowar Sadat, Mohammad Kaisarul Islam, Jakir Ahmed Chowdhury. Surface morphology and release behaviors of theophylline loaded sodium alginate gel beads. Bangladesh Pharmaceutical Journal. 13 (2), 41-46 (2010). ISSN: 0301-4606
17. Israt Nimmi, Bilquis Romana, M. Kaisarul Islam, Jakir Ahmed Chowdhury, Mia Mohammad Dulal. Sectility test on three marketed drugs act on β-receptor. Bangladesh Pharmaceutical Journal. 13 (1), 71-73 (2010). ISSN: 0301-4606
18. Ishtiaq Ahmed, Muhammad Rashedul Islam, Jakir Ahmed Chowdhury, Mohammad Kaisarul Islam, Md. Habibur Rahman. In vitro release kinetics study of naproxen from swellable hydrophilic matrix tablets. Bangladesh Pharmaceutical Journal. 13 (1), 18-22 (2010). ISSN: 0301-4606
19. Md. Saiful Islam, Ashfacur Rahman, Mohammad Kaisarul Islam, Jakir Ahmed Chowdhury and Reza-ul Jalil. Preparation and characterization of polyvinyl acetate (Kollidon® SR) microspheres containing diclofenac sodium II: Effect of core loading. Dhaka Univ. J. Pharm. Sci. 8(2), 117-122 (2009). ISSN: 1816-1839
20. Mohammad Kaisarul Islam, Mohammad Borhan Uddin, Jakir Ahmed Chowdhury. Quantitative and qualitative estimation of marketed paracetamol products in Bangladesh: I. Liquid Dosage Forms. Journal of Dhaka International University. 1(1). 185-189 (2009).
21. Chowdhury J. A., Islam M.S., Asifuzzaman Sk., Islam M.K. Antibacterial and cytotoxic activity screening of leaf extracts of Vitex negundo (Fam: Verbenaceae). J. Pharm. Sci. & Res. 1(4). 103-108 (2009). ISSN: 0975-1459
22. M. K. Islam, I. Z. Eti, and J. A. Chowdhury. Cytotoxic studies on two Meliaceae plants: Chukrasia tabularis and Aglaia roxburghiana. Journal of Scientific Research. 1 (2), 399-403 (2009). ISSN: 2070-0245

Conference Poster Presentations
1. Biphenylene and bipyridine connected benzofuran compounds as novel regulators of k-Ras transcription; 17/04/16, AACR Annual Meeting 2016, New Orleans, USA. DOI: 10.1158/1538-7445.AM2016-2914 Published July 2016
2. Identification and chemical variation of novel telomerase-targeting scaffolds to provide lead structures for development as potential anticancer agents; 10/04/13, AACR Annual Meeting 2013, Washington DC, USA.
3. Targeting key DNA/RNA heteroduplex of telomerase by small-molecule ligands; 05/07/13, Nucleic Acid Forum, Royal Society of Chemistry, UK.
4. Targeting Key DNA/RNA Heteroduplex of Telomerase by Small-molecule Ligands; October 19-23, 2013; AACR-NCI-EORTC International Conference 2013, Boston, USA. DOI: 10.1158/1535-7163.TARG-13-B204 Published November 2013
5. Targeting telomeric DNA/RNA heteroduplex by small-molecule ligands; 04/05/14, Institute of Pharmaceutical Science Research Symposium, King’s College London, UK.

Oral Presentations
1. Targeting Telomeric DNA/RNA Heteroduplex with Small-Molecule Ligands; 04/07/14, Nucleic Acid Forum, Royal Society of Chemistry, UK.
2. Design and synthesis of a small molecule scaffold targeting telomeric DNA/RNA heteroduplex in cancer cells; 26/05/15, IPS Research Symposium, King’s College London, UK.

Awards, Honors:

1. Commonwealth Scholarship in the UK (2011-2015)
2. Scholarship by Govt. of Bangladesh at undergraduate level (1998-2002)
3. Scholarship from Dhaka Education Board based on results in SSC examination (1996-1998)
4. Scholarship from BTMC based on results in class-VIII (1993-1996)


Memberships:

1. Associate Member, American Association for Cancer Research
2. Bangladesh Pharmacy Council (Reg. no: A-2674)
3. Bangladesh Pharmaceutical Society (BPS)
4. Pharmacy Graduate Association (PGA)