Biomedical subjects

Fazlul Huq

Publications and source records attributed to Fazlul Huq.

15 recordsLinked to original sources

PubMed2006

Studies on the activity of three palladium(II) compounds of the form: trans-PdL2Cl2 where L=2-hydroxypyridine, 3-hydroxypyridine, and 4-hydroxypyridine.

Three planaraminepalladium(II) complexes of the form: trans-PdCl(2)L(2), code named TH5, TH6 and TH7 where L=3-hydroxypyridine, 2-hydroxypyridine and 4-hydroxypyridine respectively have been investigated for antitumour activity against ovarian cancer cell lines: A2780, A2780(cisR) and A2780(ZD0473R). Although the compounds are generally found to be less active than cisplatin, they are often found to be more active against the resistant cell lines than the parent cell line. Among TH5, TH6 and TH7, TH6 which has two 2-hydroxypyridine non-labile ligands is found to be most active against the three cell lines. Variations in activity of TH5, TH6 and TH7 indicate that non-covalent interactions may be playing a significant role in activity. In particular, the results indicate that small changes in planaramine ligands such as the position of the polar OH group can have a more profound effect on activity of the compounds. Palladium compounds are generally found to be toxic rather tumour active because of much higher reactivity. Low but significant activity of trans-palladium(II) complexes TH5, TH6 and TH7 against the ovarian cancer cell lines indicates that it is believed to be associated with the decrease in their reactivity due to the presence of two sterically hindered planaramine ligands.

Cell Line, Tumor↗

PubMed2006

Studies on the synthesis, characterization, binding with DNA and activities of two cis-planaramineplatinum(II) complexes of the form: cis-PtL(NH3)Cl2 where L = 3-hydroxypyridine and 2,3-diaminopyridine.

BACKGROUND: Cis-planaramineplatinum(II) complexes like their trans isomers are often found to be active against cancer cell lines. The present study deals with the synthesis, characterization and determination of activity of new cis-planaramineplatinum(II) complexes. RESULTS: Two cis-planaramineplatinum(II) complexes: cis-(3-hydroxypyridine)(ammine)dichloroplatinum(II) (code named AH3) and cis-(2,3-diaminopyridine)(ammine)dichloroplatinum(II) (code named AH7) have been prepared and characterised based on elemental analyses, IR, Raman, mass and 1H NMR spectral measurements. The interactions of the compounds with pBR322 plasmid DNA have been investigated and their activity against ovarian cancer cell lines: A2780, A2780cisR and A2780ZD047Rhave been determined. Like cisplatin, AH3 and AH7 are believed to form mainly monofunctional N7(G) and bifunctional intrastrand N7(G)N7(G) adducts with DNA, causing a local distortion of a DNA strand. As a result, gel mobility of the DNA changes. Both AH3 and AH7 are found to be less active than cisplatin against the three cell lines with AH3 being the more active compound of the two. The higher activity of AH3 is in line with its lower molar conductivity value corresponding to a lower degree of dissociation. CONCLUSION: The differences in activity of AH3, AH7 and cisplatin against the cell lines illustrate structure-activity relationship.

Journal Article↗

PubMed2006

Viral etiology of pneumonia in a cohort of newborns till 24 months of age in Rural Mirzapur, Bangladesh.

Limited information is available on the etiology of acute lower respiratory infection (ALRI) particularly pneumonia in the rural community of developing countries since most etiological studies are carried out in the hospital settings. This study examined the etiology of pneumonia among young children in a rural community of Bangladesh. A cohort of 252 newborns was followed till 24 months of age during 1993-1996. Community health workers (CHWs) identified cases of ALRI during household surveillance and recommended hospitalization. On admission, nasopharyngeal aspirates (NPA) and blood were collected for bacterial and viral identification, and chest x-rays were done. Multiple regression analysis identified factors associated with a viral etiology. Physicians diagnosed 67 pneumonia; 45% of NPA were positive for viral agents of pneumonia, and respiratory syncytial virus (RSV) was predominant (81%); 6 of 48 blood cultures were positive. X-ray was done for 58 cases; 52% had pneumonic consolidation. Of the RSV cases, 33% were found in children without pneumonic consolidation. Children living in a one-room house were 3 times more likely to develop viral pneumonia (odds ratio (OR) = 3.67, CI 1.05-12.83) than children living in a larger house. Counseling on avoiding crowding where a newborn is accommodated might reduce pneumonia incidence.

Bangladesh↗

PubMed2006

Diarrheal illness in a cohort of children 0-2 years of age in rural Bangladesh: I. Incidence and risk factors.

AIM: To describe clinical characteristics and age- and season-specific incidences of diarrheal episodes, and to evaluate risk factors associated with the occurrence of diarrheal disease. METHODS: A total of 252 infants from rural Bangladesh were followed through household surveillance for 2 y from birth during the years 1993-1996. Demographic and household determinants were linked to the probability of illness using logistic regression models. RESULTS: The overall incidence of diarrhea was 4.25 episodes per child per year. Peak rates of overall, acute, and persistent diarrhea occurred in the 6-11-mo and 12-17-mo age groups. Diarrheal rates peaked during the spring and summer. Among host-related characteristics, having a sibling in the household and having had prior diarrhea were significant risk factors for diarrhea. Among environmental characteristics, spring season remained a highly statistically significant risk factor for diarrhea. CONCLUSION: Diarrheal disease continues to be a substantial burden in young children in rural Bangladesh. Most diarrheal episodes are of short duration, and should primarily be treated with oral rehydration therapy to prevent diarrhea-related mortality. Improved knowledge of oral rehydration therapy, feeding during episodes to prevent further malnutrition, prolonged breastfeeding, and the keeping of livestock in corralled areas of the home are advocated.

Bangladesh↗

PubMed2005

Synthesis, characterization, activities, cell uptake and DNA binding of trinuclear complex: [{trans-PtCl(NH(3))}(2)mu-{trans-Pt(NH(3))(2-hydroxypyridine)-(H(2)N(CH(2))(6)NH(2))(2)]Cl(4).

The trinuclear complex: [{trans-PtCl(NH(3))}(2)mu-{trans-Pt(NH(3))(2-hydroxypyridine)-(H(2)N(CH(2))(6)NH(2))(2)]Cl(4) (code named CH9) has been synthesized and characterized. The activity of the compound against human ovarian cancer cell lines: A2780, A2780(cisR) and A2780(ZD0473R), cell up take, level of binding with DNA and nature of its interaction with pBR322 plasmid DNA have been determined. Although the compound is found to be less active (about a half time as active as cisplatin) against the parent ovary cell line A2780, it is found to be more active than cisplatin against resistant cell lines: A2780(cisR) (3.6 times more) and A2780(ZD0473R) (3.4 times more). The higher activity of CH9 against the resistant cell lines suggests that the compound has been able to overcome multiple mechanisms of resistance operating in A2780(cisR) and A2780(ZD0473R) cell lines. Like other multicentered complexes, the compound is believed to form a range of interstrand GG adducts with duplex DNA that induces permanent global changes in the DNA conformation. This binding is different from that of cisplatin and ZD0473 that form mainly intrastrand adducts, inducing a local kink in a DNA strand. Increasing prevention of BamH1 digestion of form I and form II pBR322 plasmid DNA with the increase in concentration of CH9 provides support to the idea that global changes in DNA conformation are induced as a result of its interaction with the compound.

Antineoplastic Agents↗

PubMed2005

Enterotoxigenic Bacteroides fragilis-associated diarrhea in children 0-2 years of age in rural Bangladesh.

The burden of enterotoxigenic Bacteroides fragilis (ETBF)-related diarrhea was determined in a birth cohort of 252 children in rural Bangladesh. Isolation rates of ETBF in stool and risk factors for acquisition of ETBF and disease were established. Of 382 B. fragilis-positive specimens, 14.4% of the strains found in them produced enterotoxin, as determined by a tissue-culture assay. The overall isolation rate of ETBF was 2.3% (40/1750) from diarrheal specimens and 0.3% (15/5679) from nondiarrheal specimens collected throughout the 2 years of the study (P < .001). ETBF was isolated from 20.3% (40/197) of the B. fragilis-positive diarrheal specimens and from 8.1% (15/185) of the B. fragilis-positive nondiarrheal specimens (P < .001) and was significantly associated with acute diarrheal disease in children > or = 1 year of age (P = .0001). The diarrheal illness was mild in nature. In conditional multivariate analyses that examined environmental and host risk factors, the presence of livestock in the household area was linked to the acquisition of ETBF (chickens, P < .05; cows, P = .06). ETBF was found to be a small but significant contributor to diarrheal disease in this rural community. Improved management of livestock may be useful for the prevention of ETBF infection.

Age Distribution↗

PubMed2005

Synthesis, characterization and binding with DNA of four planaramineplatinum(II) complexes of the forms: trans-PtL2Cl2 and [PtL3Cl]Cl, where L = 3-hydroxypyridine, 4-hydroxypyridine and imidazo(1,2-alpha)pyridine.

Four new trans-planaramineplatinum(II) complexes, three of the form: trans-PtCl2L2, code named CH1, CH2 and CH4 where L = 3-hydroxypyridine, 4-hydroxypyridine and imidazo[1,2-alpha]pyridine, respectively, and one of the form: PtClL3, code named CH3 where L = 3-hydroxypyridine, have been prepared and characterized by elemental analyses and IR, Raman, mass and 1H NMR spectral studies. The interactions of the compounds with salmon sperm and pBR322 plasmid DNAs have been investigated and their activity against human ovarian cancer cell lines: A2780, A2780cisR and A2780ZD0473R have also been determined. The compounds are believed to form mainly monofunctional N7(G) and bifunctional intrastrand N7(G)N7(G) adducts with DNA, causing a local distortion of DNA as a result of which gel mobility of the DNA changes. The compound containing three planaramine ligands per molecule (CH3) is found to be less reactive than the compounds containing two planaramine ligands per molecule (CH1, CH2 and CH4), which in turn are less reactive than compounds containing one of the same planaramine ligands per molecule. The decrease in reactivity is reflected in lower molar conductivity values (indicating lower degree of dissociation), less pronounced changes caused to DNA conformation (indicating decreased level of platinum-DNA binding) and lower activity. The decreased reactivity of the compounds is due to a greater steric crowding produced by the bulky planaramine ligands. Changes in DNA conformation are also found to be a function of the actual nature of the planaramine ligand. The results illustrate structure-activity relationship.

Antineoplastic Agents↗

PubMed2004

Studies on the synthesis and characterization of four trans-planaramineplatinum(II) complexes of the form trans-PtL(NH3)CL2 where L = 2-hydroxypyridine, 3-hydroxypyridine, imidazole, and imidazo(1,2-alpha)pyridine.

Four trans-planaramineplatinum(II) complexes code named YH9, YH10, YH11 and YH12, each of the form trans-PtL(NH(3))Cl(2) where L = 2-hydroxypyridine and 3-hydroxypyridine, imidazole, and imidazo(1,2-alpha)pyridine for YH9, YH10, YH11 and YH12, respectively. All of the compounds have significant anticancer activity against human cancer cell lines. YH12 is found to be significantly more active than cisplatin against cisplatin-resistant ovary cell line A2780(cisR).

Cell Line, Tumor↗

PubMed2004

Synthesis, characterisation, activities, cell uptake and DNA binding of [[trans-PtCl(NH3)2] [mu-(H2N(CH2)6NH2)] [trans-PdCl(NH3)2](NO3)Cl.

The dinuclear complex: [[trans-PtCl(NH(3))(2)] [mu-(H(2)N(CH(2))(6)NH(2))] [trans-PdCl(NH(3))(2)](NO(3))Cl (code named DHD) has been synthesized and characterized. The activity against human cancer cell lines including ovarian: A2780, A2780(cisR), cell up take, level of binding with DNA and nature of interaction of the compound with pBR322 plasmid and salmon sperm DNAs have been determined. The compound is found to exhibit significant anticancer activity against ovarian cancer cell lines: A2780, A2780(cisR) and A2780(ZD0473R)--about two times as active as cisplatin against A2780 cell line, about five times as active as cisplatin against A2780(cisR) and A2780(ZD0473R) cell lines. The higher activity of DHD suggests that the compound is able to overcome multiple mechanisms of resistance operating in A2780(cisR) and A2780(ZD0473R) cell lines. DHD is believed to form a range of interstrand GG adducts with duplex DNA that induces global changes in the DNA conformation, unlike cisplatin and ZD0473 that form mainly intrastrand adducts that induces a local kink in a DNA strand. Increasing prevention of BamH1 digestion of form I and form II pBR322 plasmid DNA with the increase in concentration of DHD provides support to the idea that the interstrand binding of DHD with pBR322 plasmid DNA brings about global changes in DNA conformation.

Animals↗

PubMed2004

Studies on activities, cell uptake and DNA binding of four trans-planaramineplatinum(II) complexes of the form: trans-PtL(NH3)Cl2, where L=2-hydroxypyridine, imidazole, 3-hydroxypyridine and imidazo(1,2-alpha)pyridine.

Four trans-planaramineplatinum(II) complexes code named YH9, YH10, YH11 and YH12 each of the form trans-PtL(NH(3))Cl(2), where L=2-hydroxypyridine and 3-hydroxypyridine, imidazole, and imidazo(1,2-alpha)pyridine for YH9, YH10, YH11 and YH12, respectively, have been synthesized and the activity of the compounds against human cancer cell lines, cell uptake, DNA-binding and nature of interaction with pBR322 plasmid DNA have been studied. The compound having imidazo(1,2-alpha)pyridine ligand as one the carrier ligands in the trans-configuration is found to be significantly more active than cis-platin against ovarian A2780(cisR) cancer cell line corresponding with higher Pt-DNA binding. All other compounds have resistance factors less than that for cis-platin in the A2780 and A2780(cisR) cell lines. A greater prevention of BamH1 digestion with increasing concentration of the compounds indicates that as the compounds bind with nucleobases in DNA, the DNA conformation is changed sufficiently so as to prevent BamH1 digestion at the specific GG site. Gel electrophoresis results also indicate that as the compounds bind to DNA, unwinding of supercoiled form I DNA takes place to change it from the negatively supercoiled form I through relaxed circular form I to the positively supercoiled form I.

Antineoplastic Agents↗

PubMed2004

Studies on activities, cell up take and DNA binding of four multinuclear complexes of the form: [[trans-PtCl(NH(3))(2)](2)mu-[trans-Pd(NH(3))(2)-(H(2)N(CH(2))(n)NH(2))(2)]]Cl(4) where n=4-7.

The activity against human cancer cell lines including ovarian: A2780, A2780(cisR), cell up take, DNA-binding and nature of interaction with pBR322 plasmid DNA have been studied for four multinuclear complexes code named DH4Cl, DH5Cl, DH6Cl and DH7Cl, having the general formula: [[trans-PtCl(NH(3))(2)](2)mu-[trans-Pd(NH(3))(2)-(H(2)N(CH(2))(n)NH(2))(2)]]Cl(4) where n=4, 5, 6 and 7 for DH4Cl, DH5Cl, DH6Cl and DH7Cl, respectively. The compounds are found to exhibit significant anticancer activity against ovarian cancer cell lines: A2780, A2780(cisR) and A2780(ZD0473R). DH6Cl in which the linking diamine has six carbon atoms is found to be the most active compound. As the number of carbon atoms in the linking diamine is decreased below six and increased above six, the activity is found to decrease, illustrating structure-activity relationship. All the multinuclear compounds are believed to form a plethora of long-range interstrand GG adducts with DNA dictated by the sequence of bases in the DNA strands. Increasing prevention of BamH1 digestion with the increase in concentration of the compounds is due to global changes in DNA conformation brought about by interstrand long-range binding of the compounds with DNA.

Antineoplastic Agents↗

PubMed2002

Studies on the interaction between Ag(+) and DNA.

The interaction between silver ion and DNA has been followed by submarine gel electrophoresis. When pBR322 plasmid DNA was allowed to interact with silver(I) acetate, it was found to contain Form I and Form II bands whose intensity remained unchanged as the concentration of Ag(+) was increased from 0 to 50 mM. However, the mobility of the bands decreased as the concentration of Ag(+) was increased, indicating the occurrence of increased covalent binding of the metal ion with DNA. When 1:1 mixtures of silver(I) acetate and ascorbate were allowed to interact with plasmid and genomic DNAs, it was found that the mixtures were much more damaging to plasmid as well as genomic DNAs than silver(I) acetate or ascorbate alone. In the case of pBR322 plasmid DNA, the mixture at 12.5 mM concentration was found to be more damaging than the mixtures at both higher and lower concentrations. The increased DNA damage is believed to be due to free radicals produced from the oxidation of ascorbate by molecular oxygen where the metal ion was playing a catalytic role.

Acetates↗

PubMed2002

Studies on the interaction between Cd(2+) ions and nucleobases and nucleotides.

Adenine↗

PubMed2002

Studies on the interaction between Cd(2+) ions and DNA.

Cadmium is a potent carcinogen in rodents and has recently been accepted by the International Agency for Research on Cancer as a category 1 (human) carcinogen, but the molecular mechanism of its action remains largely unclear. It has however been suggested that cadmium-induced carcinogenesis may involve either direct or indirect interaction of Cd(2+) with DNA. Cd(2+) is believed to bind covalently with N7 centres of adenine and guanine. At low concentrations (< or =50 mM), Cd(2+) is found to react with plasmid DNA to produce a mixture of Form I and Form II bands whereas at higher concentrations (> or =100 mM), Cd(2+) causes extensive damage to DNA at a pH 5.8 solution of cadmium nitrate. Within the range 0-100 mM (when pH is adjusted to 7.4 by adding NaOH) an increase in concentration of Cd(2+) is found to cause a decrease in the gel mobility rate of plasmid and an increase in the intensity of the Form II band. When plasmid DNA is digested with BamH1, only the Form III band is observed both in the presence and absence of Cd(2+). However, the mobility of the band is found to decrease with the increase in the concentration of Cd(2+). When the enzyme Ssp1 which cuts plasmid DNA at the AT sites is used instead of BamH1, two bands are observed in the presence of cadmium as against one band in the absence of cadmium. These results suggest that Cd(2+) binds covalently with DNA (possibly at G, A and T centres) and can form intrastrand bifunctional AT adducts but not the GG adducts. It may also be that neither GG nor AT adducts are formed and yet Ssp1 digestion is prevented because of a structural modification introduced in adenine by its interaction with Cd(2+). In the presence of antioxidants such as cysteine, glutathione and ascorbate (especially cysteine and ascorbate), DNA damage is found to be greater than expected for the combined effects of the antioxidant and Cd(2+). The increased DNA damage is believed to be due to the formation of reactive oxygen species (ROS).

Animals↗

PubMed2002

Molecular modeling analysis: "Why is 2-hydroxypyridine soluble in water but not 3-hydroxypyridine?".

Molecular mechanics and semiempirical calculations using HyperChem 5 were carried out to investigate whether the results obtained can explain why 2-hydroxypyridine is far more soluble in water than 3-hydroxypyridine. The results of molecular mechanics calculations show that in solution in water the total energy of 2-hydroxypyridine in the oxo form is less than that of 3-hydroxypyridine in the zwitterionic form by 2.14 kcal x mol(-1). The difference is much greater for the AM1 optimized H-bonded molecules. The greater amount of energy released in dissolution and H-bond formation by 2-hydroxypyridine than by 3-hydroxypyridine together with a higher crystal lattice energy for the latter provide an explanation as to why 3-hydroxypyridine is much less soluble in water than 2-hydroxypyridine. When the predicted electronic spectral lines of the compounds were compared with the observed lambda(max) values, it is found that generally the results obtained using AM1 agree more closely with the experimentally observed values.

Antineoplastic Agents↗